WO1999065337A1 - Dietary supplement for post-menopausal women - Google Patents

Dietary supplement for post-menopausal women Download PDF

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Publication number
WO1999065337A1
WO1999065337A1 PCT/US1999/013676 US9913676W WO9965337A1 WO 1999065337 A1 WO1999065337 A1 WO 1999065337A1 US 9913676 W US9913676 W US 9913676W WO 9965337 A1 WO9965337 A1 WO 9965337A1
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WO
WIPO (PCT)
Prior art keywords
vitamin
per day
dietary
dietary supplement
calcium
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PCT/US1999/013676
Other languages
French (fr)
Inventor
Stacey J. Bell
Bruce R. Bistrian
R. Armour Forse
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Beth Israel Deaconess Medical Center
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Application filed by Beth Israel Deaconess Medical Center filed Critical Beth Israel Deaconess Medical Center
Priority to AU45738/99A priority Critical patent/AU4573899A/en
Publication of WO1999065337A1 publication Critical patent/WO1999065337A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A23L33/11—Plant sterols or derivatives thereof, e.g. phytosterols
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/15—Vitamins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/16—Inorganic salts, minerals or trace elements
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/06—Fungi, e.g. yeasts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
    • A61K36/8998—Hordeum (barley)
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • Post-menopausal women are at risk of osteoporosis and coronary heart disease (CHD), among other health conditions.
  • CHD coronary heart disease
  • Proper nutritional support for post menopausal women may mitigate or reduce risk factors that result in disease.
  • Coronary heart disease is a major cause of death in women. It claims tne lives of nearly 250,000 women per year, most of whom are post-menopausal. Although generally not manifest until the post-menopausal stage, CHD develops over decades. Well established risk factors for CHD include elevated plasma cholesterol levels and abnormal glucose metabolism. Also implicated in the development of CHD are elevated homocysteine levels and the effects of free radicals. Phytoestxogens, antioxidants, chromium and folic acid have been shown to mitigate these risk factors.
  • Osteoporosis is associated with the aging process and predominantly affects women. It is characterized by diminished bone density, which results in increased bone fractures and vertebral column collapse. Bone loss begins around about age 35. This loss accelerates during the menopause, which generally occurs around age 45 to 55. Osteoporosis develops over decades and is related to peak bone mass, as well as to the degree of bone loss. Adequate calcium intake limits the development of osteoporosis. Moreover, certain vitamins and minerals enhance calcium absorption and utilization.
  • the invention pertains to a dietary supplement for the purpose of supplementing the micronutrient needs of post-menopausal women for the prevention or reduction of osteoporosis and osteoporetic fractures associated therewith, and coronary heart disease, by retarding bone loss and improving the cardiovascular health of the post-menopausal woman. Bone and cardiovascular health can be maintained by the routine administration of the dietary supplements described herein.
  • a dietary supplement of this invention comprises phytoestrogen, calcium and vitamin D present in amounts sufficient to minimize bone loss in a post- menopausal woman; dietary fiber, vitamin B 12 , vitamin B 6 , and folic acid present in amounts sufficient to reduce total serum cholesterol and low density lipoprotein cholesterol; and optionally physiologically acceptable vehicle(s).
  • the dietary fiber can be any soluble fiber (e.g., derived from yeast or plant, such as oat and barley) that ferments in the colon.
  • the dietary fiber can be ⁇ -glucans which can be soluble in part and insoluble in part, such as whole yeast glucan particles which are most preferred.
  • Members of the isoflavone class of phytoestrogens e.g., genistein, daidzein and glycitein are particularly preferred.
  • the dietary supplements of this invention may be formulated as a tablet, capsule, powder, suspension, gel or liquid, and are preferably formulated for a single or multiple daily administration.
  • the nutritional supplement can be provided in a variety of forms, such as baked goods, puddings, confections, snack foods, ice cream, frozen confections and novelties, dietary beverages, or non-baked extruded foods such as dietary bars.
  • the invention also pertains to methods for supplementing the dietary needs and preventing or reducing health risks associated with bone loss and cardiovascular disease in post-menopausal women.
  • the method comprises administering to a post- menopausal woman an effective amount of the dietary supplement of this invention preferably throughout the remainder of the woman's life, to prevent or reduce bone loss and osteoporotic effects associated therewith; to lower serum cholesterol levels; to reduce levels of low density lipoprotein cholesterol and elevate high density lipoprotein cholesterol; or to prevent or reduce the risk of coronary heart disease.
  • the dietary supplements and the methods of this invention can also be used for women who have defective nonfunctioning ovaries or who lack ovaries since they have similar health risks due to hormonal changes, for instance.
  • the dietary supplement is formulated to supplement the increased nutritional needs of post-menopausal women for the prevention or reduction of the risk of coronary heart disease and osteoporosis throughout this stage of a woman's life.
  • post-menopause as the term is used herein is characterized by complete cessation of ovarian function and an increase in the incidence of osteoporotic fracture and coronary heart disease.
  • the dietary supplemental comprises calcium, vitamin D and phytoestrogens present in amounts sufficient to minimize bone loss in a post-menopausal woman; and vitamin B 12 , vitamin B 6 , folic acid and dietary fiber present in an amount sufficient to reduce total serum cholesterol and low density lipoprotein cholesterol; and optionally in an admixture with physiologically acceptable vehicle(s).
  • a dietary supplement formulated in single or multiple units, provides from about 1 mg to about 2000 mg calcium per day; from about 1 ⁇ g to about 20 ⁇ g vitamin D per day; from about 1 mg to about 100 mg isoflavone per day; from about 1 g to about 50 g ⁇ -glucan per day; from about 1 ⁇ g to about 2000 ⁇ g vitamin B 12 per day; from about 1 mg to about 100 mg vitamin B 6 per day; and from about 1 ⁇ g to about 1000 ⁇ g folic acid per day.
  • a dietary supplement in single or multiple units, provides from about 500 mg to about 1500 mg calcium per day; from about 5 ⁇ g to about 13 ⁇ g vitamin D per day; from about 20 mg to about 60 mg isoflavone per day; from about 1.5 ⁇ g to about 4.0 ⁇ g vitamin B 12 per day; from about 1.6 mg to about 4.6 mg vitamin B 6 per day; and from about 180 ⁇ g to about 800 ⁇ g folic acid per day.
  • the invention also pertains to a method for supplementing the dietary needs and preventing or reducing life stage associated health risks in post-menopausal women.
  • This method comprises administering (preferably on a daily basis) to a post-menopausal woman an "effective amount" of the dietary supplement of the invention throughout that life stage.
  • effective amount means an amount of the dietary supplement and components contained therein (e.g., either singly or in combination) sufficient to achieve a desired effect, i.e., to prevent or reduce certain health risks in post-menopausal women.
  • the methods of this invention and the term "effective amount" is intended to embrace therapeutic and prophylactic treatment.
  • the dietary supplements of this invention are not meant to replace a well-balanced diet, but are instead intended to supplement a prudent diet. Unlike known broad-based dietary supplements, this invention does not merely provide the prescribed Recommended Daily Allowance (RDA) of micronutrients, but rather is geared to emphasize the disease prevention properties of micronutrient supplementation. Thus, cumulative beneficial and preventive effects should be achieved by dietary supplementation with the appropriate dietary supplement of the invention.
  • RDA Recommended Daily Allowance
  • the dietary supplements of this invention contain vitamins, minerals and other compounds that are specifically included in effective amounts to address common health concerns that arise during post-menopause. Moreover, the dietary supplements are formulated to prevent or to lessen the risk of osteoporosis, osteoporotic fractures associated therewith, and coronary heart disease, which are generally manifest in the post-menopause life stage.
  • the dietary supplement and the methods of this invention can also be used for women who lack ovaries or who have defective, nonfunctioning ovaries (e.g., hormone levels below normal).
  • the presence of calcium and vitamin D in the dietary supplement of this invention is intended to retard the rate at which bone degrades, thereby minimizing the onset and debilitating effects of osteoporosis.
  • Osteoporosis is the nonvolitional loss of bone that results in an increased susceptibility to fracture, especially of the wrist, lumbar spine and hip region.
  • At menopause there is an increase in the amount of calcium lost in the urine (Christopher, B.E., "Calcium and Osteoporosis", Nutrition 75:664-686 (1997).
  • the absorption of calcium may be diminished.
  • the amount of calcium included in the dietary supplements of this invention will depend, in part, on the physical and nutritional condition of the post- menopausal woman, whether the individual is undergoing hormone replacement therapy, as well as the type of calcium used.
  • the amount of calcium will be from about 1 to about 2,000 mg per day; preferably 500 to 1,500 mg per day, with 1,200 mg being optimal as recommended by the Institute of Medicine in the Dietary Reference Intake Guideline of 1997.
  • the calcium may be derived from calcium carbonate, calcium citrate, calcium phosphate, calcium maleate, calcium lactate maleate, calcium lactate-gluconate, or a combination thereof; with calcium citrate or calcium maleate being most preferred.
  • Vitamin D (1,25-dihydroxyvitamin D 3 ) when administered with calcium or calcitonin has been shown to prevent bone loss in women who had a prolonged use of corticosteroids, which had led to bone loss in the lumbar spine (Sambrook et al., N. Engl. J. Med., 328:1141-52 (1993)).
  • Vitamin D is incorporated in the dietary supplement as vitamin D 2 (ergocholecaliferol), vitamin D 3 (cholecalciferol, calcitriol), calcifediol [25(OH)] or combination thereof.
  • the dietary supplement should provide from about 1 to about 20 micrograms per day of vitamin D; preferably from about 5 to about 13 micrograms per day (400 to 800 I.U.). Most preferably, vitamin D will be present in the dietary supplement in the recommended daily allowance (RDA) of about 5 micrograms per day.
  • RDA recommended daily allowance
  • Phytoestrogens and more particularly isofiavones are included in the dietary supplements of this invention. These compounds have been demonstrated by clinical trials to modulate the menstrual cycle, reduce menopausal symptoms, and lower LDL cholesterol (LDL-C) levels. J. Nutr., 1996, 126(1): 161-7; N. Engl. J. Med., 1995, 333:276-82. Epidemiologic observations indicate women in countries where diets are high in phytoestrogen (averaging about 40-50 mg/day) have a decreased incidence of breast cancer, menopausal symptoms and osteoporosis. Nutr. Cancer, 1994, 21 :113-131 ; J. Nutr., 1995, 125; 151S-110S; Am.
  • Isofiavones or isoflavanoids are a class of phytoestrogens derived from plants, commonly soy beans. The plant source is not critical, however, soybeans are an excellent source of isofiavones and are particularly abundant in genistein.
  • phytoestrogens such as genistin, glycitin and diadzin contain a glycosidic moiety, whereas other phytoestrogens are nonglycosylated, genistein, glycitein and diadzein.
  • Phytoestrogens obtained from a single plant generally are a mixture of both glycosylated and nonglycosylated forms.
  • the dietary supplements of the invention generally contain a mixture of phytoestrogens; however, purified phytoestrogens may be used.
  • Daidzein is a metabolite of ipriflavone which has been shown to increase bone mass.
  • Soy isofiavones have estrogenic effects, which are mediated through estrogen receptors.
  • Soy isofiavones are weaker than estradiol and diethylstilbestrol.
  • genistein is known to be an estrogen analog and will bind to estrogen receptors with the affinity of 0.2% of estradiol, the major circulating estrogen (Erdman JW, Potter SM. Soy and bone health. The Soy Connection volume 5, 1997).
  • the isofiavones have antiestrogenic effects rather than estrogenic effects. It usually depends upon the particular tissue how the isofiavones behaves. In the case of bone, isofiavones have estrogenic action or are estrogen agonists and should improve bone health.
  • the isoflavone genistein
  • tyrosine kinase an enzyme important in the mechanism leading to platelet aggregation and blood clotting. Ingestion of this isoflavone or soy protein may help to decrease thrombosis and prevent mortality from cardiovascular disease (Kurowska EM. Soy and reduced risk of cardiovascular disease. The Soy Connection, vol. 5, page 1, 1997).
  • Soy may also prevent breast cancer and hot flashes that occur during menopause.
  • Genistein and diadzein have been shown to inhibit human breast cancer and prostate cancer cell lines in cultures by mechanisms independent of steroid binding (ADM, Technical Report, 1998).
  • Isofiavones may exert their effect by inhibiting tumor growth and inducing cell maturation.
  • Chinese women who are pre- menopausal have a reduced incidence of breast cancer compared to women in other cultures where soy is not consumed regularly. This phenomenon has been shown to be true for women in Australia who eat a high soy diet and women in other parts of Southeast Asia.
  • phytoestrogen levels of from about 1 to about 100 mg per day, preferably from about 20 to about 60 mg per day, and most preferably about 50 mg per day, provide women with phytoestrogen levels that are physiologically effective and may be used to supplement women's micronutrient needs during post-menopause.
  • the phytoestrogen can be selected from the group consisting of genistin, glycitin, diadzin, genistein, glycitein, diadzein and combinations thereof.
  • a preferred mixture of phytoestrogen may be obtained commercially such as Novasoy (genistein: daidzein: glycitein in a ratio of 1.1 : 1 :0.2) from Archer Daniels Midland (ADM). DIETARY FIBER
  • Dietary fiber suitable for reducing total serum cholesterol and low density lipoprotein cholesterol is also incorporated in the dietary supplement of the present invention.
  • the dietary fiber can be any soluble fiber (e.g., derived from yeast or plant, such as oat and barley) that ferments in the colon.
  • suitable dietary fiber include but are not limited to, nondigestible polysaccharides, plant cell walls, carageenans, mucilages, glucans (e.g., ⁇ -glucans), gums, agar, some hemicelluloses, psyllium and pectin.
  • the dietary fiber can be a ⁇ - glucan which is soluble in part and insoluble in part, such as whole yeast glucan particles which are most preferred.
  • Yeast ⁇ -glucan has been shown to reduce serum cholesterol and LDL-C concentrations and raise high density lipoprotein cholesterol levels. See U.S. Patent No. 4,962,094; the entire teachings of which are incorporated herein by reference.
  • Hypercholesterolemic subjects > 240 mg/dL
  • Subjects received 15 grams of yeast ⁇ -glucan (FibercelTM, Alpha-Beta Technology, Inc.; whole yeast glucan particles having an in vivo glucan morphology ) in orange juice for eight weeks.
  • the amount of dietary fiber included in the dietary supplement of this invention will vary depending upon the source and type of fiber incorporated therein, but in any event, should be an amount sufficient to reduce total serum cholesterol and low density lipoprotein cholesterol.
  • Dietary fiber can be incorporated into the dietary supplement in amounts of from about 1 g to about 50 gm day; with preferably from about 5 g to about 20 gm/day; most preferably 15 gm day.
  • a particularly preferred dietary is yeast ⁇ -glucan, such as that described in U.S. Patent No. 4,962,094 (FibercelTM).
  • Vitamin B 12 (cyanocobalamin), vitamin B 6 (pyridoxine) and folic acid are included in the dietary supplement of this invention. These elements act synergistically to reduce serum homocysteine; high levels of which are associated with coronary heart disease.
  • the amount of vitamin B 12 is from about 1 to about 2,000 mg/day, preferably from about 1.5 to about 4.0 ⁇ g/day, with 2.0 ⁇ g/day being optimal.
  • Folic acid is provided in the dietary supplement as it has been shown to have beneficial cardiac effects and to decrease the risk of cervical dysplasia. Scand. J. Clin. Lab Invest., 1988, 48:215-221.
  • the dietary supplements of the invention are intended to be orally administered daily. Preferably, they are formulated for single daily administration, but may be formulated in multiple portions or as time release compositions for more or less frequent administration; for example, the dietary supplement may be formulated as two tablets for twice daily administration. For reasons of size (ease of swallowing) or improved bioabsorption or utilization (e.g., before or after a meal or before sleep), a given dosage may be divided into two, three, or more tablets (or capsules, etc.). A daily dosage may be administered as one tablet, as two tablets taken together, or as two tablets taken separately (e.g., one in the morning and one in the evening).
  • the recommended daily amounts of each ingredient, as described above, serve as a guideline for formulating the dietaiy supplements of this invention.
  • the actual amount of each ingredient per unit dosage will depend upon the number of units daily administered to the post-menopausal woman. This is a matter of product design and is well within the skill of the dietary supplement formulator.
  • the dietary supplements of the present invention may be formulated using any pharmaceutically acceptable forms of the vitamins, minerals and other nutrients discussed above, including their salts. They may be formulated into capsules, tablets, powders, suspensions, gels or liquids optionally comprising a physiologically acceptable carrier, such as but not limited to water, milk, juice, starch, vegetable oils, salt solutions, hydro xym ethyl cellulose, carbohydrate.
  • the dietary supplements may be formulated as powders, for example, for mixing with consumable liquids, such as milk, juice, water or consumable gels or syrups for mixing into other dietary liquids or foods.
  • the dietary supplements of this invention may be formulated with other foods or liquids to provide premeasured supplemental foods, such as single servings bars, for example.
  • the dietary supplement can be made in a variety of forms, such as baked goods, (e.g., cookies, brownies, fudge, cake, breads, biscuits, crackers,), puddings, confections, (i.e., candy), snack foods (e.g., pretzels, chips), dietary beverages, ice cream, frozen confections and novelties, or non-baked, extruded food products such as bars.
  • baked goods e.g., cookies, brownies, fudge, cake, breads, biscuits, crackers
  • puddings e.g., candy
  • snack foods e.g., pretzels, chips
  • dietary beverages e.g., ice cream, frozen confections and novelties
  • non-baked extruded food products such as bars.
  • the preferred form is a non-baked extruded nutritional bar.
  • the dietary supplement can also contain other ingredients such as one or a combination of other vitamins, minerals, antioxidants, fiber and other dietary supplements. Selection of one or several of these ingredients is a matter of formulation design, consumer and end-user preference .
  • the amount of these ingredients added to the dietary supplements of this invention are readily known to the skilled artisan and guidance to such amounts can be provided by the U.S. RDA doses for children and adults.
  • Vitamins and minerals that can be added include, but are not limited to, calcium phosphate or acetate, tribasic; potassium phosphate, dibasic; magnesium sulfate or oxide; salt (sodium chloride); potassium chloride or acetate; ascorbic acid; ferric orthophosphate; niacinamide; zinc sulfate or oxide; calcium pantothenate; copper gluconate; riboflavin; beta-carotene; pyridoxine hydrochloride; thiamin mononitrate; folic acid; biotin; chromium chloride or picolonate; potassium iodide; sodium selenate; sodium molybdate; phylloquinone; Vitamin D 3 ; cyanocobalamin; sodium selenite; copper sulfate; Vitamin A; Vitamin E; vitamin B 6 and hydrochloride thereof; Vitamin C; inositol; Vitamin B 12 ; potassium iodide.
  • the dietary supplement can comprise one or a combination of antioxidants in therapeutic amounts.
  • Antioxidants suitable for use in this invention include but are not limited to, vitamin, A, vitamin C, vitamin E, ⁇ -carotene, zinc, chromium, selenium and herbs, such as ginkgo biloba, ginseing.
  • the amount of antioxidant(s) per unit serving are a matter of design and will depend upon the total number of unit servings of the dietary supplement daily administered to the patient. The total amount of antioxidant(s) will also depend, in part, upon the condition of the patient. Preferably the amount of antioxidant(s) will be a fraction or multiplier of the RDA amounts.
  • the dietary supplement will comprise 50% RDA antioxidants per unit dosage and the patient will consume two units per day.
  • Flavors, coloring agents, spices, nuts and the like can be incorporated into the product.
  • Flavorings can be in the form of flavored extracts, volatile oils, chocolate flavorings, peanut butter flavoring, cookie crumbs, crisp rice, vanilla or any commercially available flavoring.
  • useful flavorings include but are not limited to pure anise extract, imitation banana extract, imitation cherry extract, chocolate extract, pure lemon extract, pure orange extract, pure peppermint extract, imitation pineapple extract, imitation rum extract, imitation strawberry extract, or pure vanilla extract; or volatile oils, such as balm oil, bay oil, bergamot oil, cedarwood oil, cherry oil, walnut oil, cinnamon oil, clove oil, or peppermint oil; peanut butter, chocolate flavoring, vanilla cookie crumb, butterscotch or toffee.
  • the dietary supplement contains cocoa ro chocolate.
  • Emulsifiers may be added for stability of the final product.
  • suitable emulsifiers include, but are not limited to, lecithin (e.g., from egg or soy), and/or mono- and di-glycerides.
  • Other emulsifiers are readily apparent to the skilled artisan and selection of suitable emulsifier(s) will depend, in part, upon the formulation and final product.
  • Preservatives may also be added to the dietary supplement to extend product shelf life.
  • preservatives such as potassium sorbate, sodium sorbate, potassium benzoate, sodium benzoate or calcium disodium EDTA are used.
  • the dietary supplement can contain artificial sweeteners, e.g., saccharides, cyclamates, aspartamine, aspartame, acesulfame K, and/or sorbitol.
  • artificial sweeteners e.g., saccharides, cyclamates, aspartamine, aspartame, acesulfame K, and/or sorbitol.
  • Such artificial sweeteners can be desirable if the dietary supplement is intended for an overweight or obese individual, or an individual with type II diabetes who is prone to hyperglycemia.
  • the liquid ingredients are cooked; the dry ingredients are added with the liquid ingredients in a mixer and mixed until the dough phase is reached; the dough is put into an extruded, and extruded; the extruded dough is cut into appropriate lengths; and the product is cooled.
  • the ingredients comprising the dietary supplement of this invention can be added to traditional formulations or they can be used to replace traditional ingredients. Those skilled in food formulating will be able to design appropriate foods/beverages with the objective of this invention in mind.

Abstract

Bone and cardiovascular health can be maintained by the routine administration of the dietary supplements described herein. A dietary supplement of this invention comprises calcium, phytoestrogen and vitamin D present in amounts sufficient to minimize bone loss in a post-menopausal woman; and dietary fiber, vitamin B12, vitamin B6 and folic acid present in amounts sufficient to reduce total serum cholesterol and low density lipoprotein cholesterol. The dietary supplement and methods are also useful for women lacking their ovaries or having defective ovaries.

Description

DIETARY SUPPLEMENT FOR POST-MENOPAUSAL WOMEN
RELATED APPLICATIONS
This application claims priority to U.S. Serial No. 09/100,388, filed June 19, 1998, the contents of which are incorporated herein by reference.
BACKGROUND OF THE INVENTION
Post-menopausal women are at risk of osteoporosis and coronary heart disease (CHD), among other health conditions. Proper nutritional support for post menopausal women may mitigate or reduce risk factors that result in disease.
Coronary heart disease is a major cause of death in women. It claims tne lives of nearly 250,000 women per year, most of whom are post-menopausal. Although generally not manifest until the post-menopausal stage, CHD develops over decades. Well established risk factors for CHD include elevated plasma cholesterol levels and abnormal glucose metabolism. Also implicated in the development of CHD are elevated homocysteine levels and the effects of free radicals. Phytoestxogens, antioxidants, chromium and folic acid have been shown to mitigate these risk factors.
Osteoporosis is associated with the aging process and predominantly affects women. It is characterized by diminished bone density, which results in increased bone fractures and vertebral column collapse. Bone loss begins around about age 35. This loss accelerates during the menopause, which generally occurs around age 45 to 55. Osteoporosis develops over decades and is related to peak bone mass, as well as to the degree of bone loss. Adequate calcium intake limits the development of osteoporosis. Moreover, certain vitamins and minerals enhance calcium absorption and utilization.
SUMMARY OF THE INVENTION
The invention pertains to a dietary supplement for the purpose of supplementing the micronutrient needs of post-menopausal women for the prevention or reduction of osteoporosis and osteoporetic fractures associated therewith, and coronary heart disease, by retarding bone loss and improving the cardiovascular health of the post-menopausal woman. Bone and cardiovascular health can be maintained by the routine administration of the dietary supplements described herein. A dietary supplement of this invention comprises phytoestrogen, calcium and vitamin D present in amounts sufficient to minimize bone loss in a post- menopausal woman; dietary fiber, vitamin B12, vitamin B6, and folic acid present in amounts sufficient to reduce total serum cholesterol and low density lipoprotein cholesterol; and optionally physiologically acceptable vehicle(s). The dietary fiber can be any soluble fiber (e.g., derived from yeast or plant, such as oat and barley) that ferments in the colon. Alternatively, the dietary fiber can be β-glucans which can be soluble in part and insoluble in part, such as whole yeast glucan particles which are most preferred. Members of the isoflavone class of phytoestrogens (e.g., genistein, daidzein and glycitein) are particularly preferred.
The dietary supplements of this invention may be formulated as a tablet, capsule, powder, suspension, gel or liquid, and are preferably formulated for a single or multiple daily administration. Alternatively, the nutritional supplement can be provided in a variety of forms, such as baked goods, puddings, confections, snack foods, ice cream, frozen confections and novelties, dietary beverages, or non-baked extruded foods such as dietary bars.
The invention also pertains to methods for supplementing the dietary needs and preventing or reducing health risks associated with bone loss and cardiovascular disease in post-menopausal women. The method comprises administering to a post- menopausal woman an effective amount of the dietary supplement of this invention preferably throughout the remainder of the woman's life, to prevent or reduce bone loss and osteoporotic effects associated therewith; to lower serum cholesterol levels; to reduce levels of low density lipoprotein cholesterol and elevate high density lipoprotein cholesterol; or to prevent or reduce the risk of coronary heart disease. The dietary supplements and the methods of this invention can also be used for women who have defective nonfunctioning ovaries or who lack ovaries since they have similar health risks due to hormonal changes, for instance.
DETAILED DESCRIPTION OF THE INVENTION The dietary supplement is formulated to supplement the increased nutritional needs of post-menopausal women for the prevention or reduction of the risk of coronary heart disease and osteoporosis throughout this stage of a woman's life. For purposes of this invention, "post-menopause" as the term is used herein is characterized by complete cessation of ovarian function and an increase in the incidence of osteoporotic fracture and coronary heart disease. The dietary supplemental comprises calcium, vitamin D and phytoestrogens present in amounts sufficient to minimize bone loss in a post-menopausal woman; and vitamin B12, vitamin B6, folic acid and dietary fiber present in an amount sufficient to reduce total serum cholesterol and low density lipoprotein cholesterol; and optionally in an admixture with physiologically acceptable vehicle(s). In a preferred embodiment, a dietary supplement, formulated in single or multiple units, provides from about 1 mg to about 2000 mg calcium per day; from about 1 μg to about 20 μg vitamin D per day; from about 1 mg to about 100 mg isoflavone per day; from about 1 g to about 50 g β-glucan per day; from about 1 μg to about 2000 μg vitamin B12 per day; from about 1 mg to about 100 mg vitamin B6 per day; and from about 1 μg to about 1000 μg folic acid per day. In another embodiment, a dietary supplement, formulated in single or multiple units, provides from about 500 mg to about 1500 mg calcium per day; from about 5 μg to about 13 μg vitamin D per day; from about 20 mg to about 60 mg isoflavone per day; from about 1.5 μg to about 4.0 μg vitamin B12 per day; from about 1.6 mg to about 4.6 mg vitamin B6 per day; and from about 180 μg to about 800 μg folic acid per day.
The invention also pertains to a method for supplementing the dietary needs and preventing or reducing life stage associated health risks in post-menopausal women. This method comprises administering (preferably on a daily basis) to a post-menopausal woman an "effective amount" of the dietary supplement of the invention throughout that life stage. The term "effective amount", as used herein, means an amount of the dietary supplement and components contained therein (e.g., either singly or in combination) sufficient to achieve a desired effect, i.e., to prevent or reduce certain health risks in post-menopausal women. The methods of this invention and the term "effective amount" is intended to embrace therapeutic and prophylactic treatment. The dietary supplements of this invention are not meant to replace a well-balanced diet, but are instead intended to supplement a prudent diet. Unlike known broad-based dietary supplements, this invention does not merely provide the prescribed Recommended Daily Allowance (RDA) of micronutrients, but rather is geared to emphasize the disease prevention properties of micronutrient supplementation. Thus, cumulative beneficial and preventive effects should be achieved by dietary supplementation with the appropriate dietary supplement of the invention.
The dietary supplements of this invention contain vitamins, minerals and other compounds that are specifically included in effective amounts to address common health concerns that arise during post-menopause. Moreover, the dietary supplements are formulated to prevent or to lessen the risk of osteoporosis, osteoporotic fractures associated therewith, and coronary heart disease, which are generally manifest in the post-menopause life stage. The dietary supplement and the methods of this invention can also be used for women who lack ovaries or who have defective, nonfunctioning ovaries (e.g., hormone levels below normal).
Each of the components that are incorporated into the dietary supplement are described in detail below under separate headings. Briefly, calcium, vitamin D and phytoestrogen are incorporated into the dietary supplement to mitigate bone loss in the post-menopausal woman. Dietary fiber, vitamin B12, vitamin B6 and folate are intended to prophylatically reduce the risks of coronary heart disease, for instance by reducing serum cholesterol and low density lipoprotein cholesterol and raising levels of high density lipoprotein cholesterol.
CALCIUM AND VITAMIN D
The presence of calcium and vitamin D in the dietary supplement of this invention is intended to retard the rate at which bone degrades, thereby minimizing the onset and debilitating effects of osteoporosis. Osteoporosis is the nonvolitional loss of bone that results in an increased susceptibility to fracture, especially of the wrist, lumbar spine and hip region. At menopause, there is an increase in the amount of calcium lost in the urine (Christopher, B.E., "Calcium and Osteoporosis", Nutrition 75:664-686 (1997). In addition, the absorption of calcium may be diminished. These two factors coupled together indicate that the intake of calcium should increase with age to at least 1,200 mg per day. Studies using calcium to retard bone loss in aging women suggest that treatment with calcium slowed the rate of bone loss from 1.0% per year (controls without calcium) to 0.014%o in the treatment group (not significantly different). Vitamin D deficiency in the elderly also contributes to bone loss. The form of calcium supplementation has also been shown to effect the rate of bone loss. For example, calcium maleate has been shown to work better than calcium carbonate (Dawson-Hughes, N. Engl. J. Med., 323:818- 83 (1990)).
The amount of calcium included in the dietary supplements of this invention will depend, in part, on the physical and nutritional condition of the post- menopausal woman, whether the individual is undergoing hormone replacement therapy, as well as the type of calcium used. The amount of calcium will be from about 1 to about 2,000 mg per day; preferably 500 to 1,500 mg per day, with 1,200 mg being optimal as recommended by the Institute of Medicine in the Dietary Reference Intake Guideline of 1997. The calcium may be derived from calcium carbonate, calcium citrate, calcium phosphate, calcium maleate, calcium lactate maleate, calcium lactate-gluconate, or a combination thereof; with calcium citrate or calcium maleate being most preferred.
Vitamin D (1,25-dihydroxyvitamin D3 ) when administered with calcium or calcitonin has been shown to prevent bone loss in women who had a prolonged use of corticosteroids, which had led to bone loss in the lumbar spine (Sambrook et al., N. Engl. J. Med., 328:1141-52 (1993)). Vitamin D is incorporated in the dietary supplement as vitamin D2 (ergocholecaliferol), vitamin D3 (cholecalciferol, calcitriol), calcifediol [25(OH)] or combination thereof. The dietary supplement should provide from about 1 to about 20 micrograms per day of vitamin D; preferably from about 5 to about 13 micrograms per day (400 to 800 I.U.). Most preferably, vitamin D will be present in the dietary supplement in the recommended daily allowance (RDA) of about 5 micrograms per day.
PHYTOESTROGEΝS/ISOFLAVOΝES
Phytoestrogens and more particularly isofiavones are included in the dietary supplements of this invention. These compounds have been demonstrated by clinical trials to modulate the menstrual cycle, reduce menopausal symptoms, and lower LDL cholesterol (LDL-C) levels. J. Nutr., 1996, 126(1): 161-7; N. Engl. J. Med., 1995, 333:276-82. Epidemiologic observations indicate women in countries where diets are high in phytoestrogen (averaging about 40-50 mg/day) have a decreased incidence of breast cancer, menopausal symptoms and osteoporosis. Nutr. Cancer, 1994, 21 :113-131 ; J. Nutr., 1995, 125; 151S-110S; Am. J. Clin. Nutr. 1995, 62: 645. Animal studies have provided a biological basis for these observations. J. Ster. Biochem & Mol. Biol, 1992, 41 (3-8): 331-7; First International Symposium on the role of Soy and Preventing and Treating Chronic Disease (1994), Speaker Abstracts. There is increasing evidence that the beneficial effects of soy are attributable to its isoflavone content. Isofiavones or isoflavanoids are a class of phytoestrogens derived from plants, commonly soy beans. The plant source is not critical, however, soybeans are an excellent source of isofiavones and are particularly abundant in genistein. Some phytoestrogens, such as genistin, glycitin and diadzin contain a glycosidic moiety, whereas other phytoestrogens are nonglycosylated, genistein, glycitein and diadzein. Phytoestrogens obtained from a single plant generally are a mixture of both glycosylated and nonglycosylated forms. The dietary supplements of the invention generally contain a mixture of phytoestrogens; however, purified phytoestrogens may be used. Daidzein is a metabolite of ipriflavone which has been shown to increase bone mass. Animal and clinical data suggest that diets containing soy protein or the isolated isofiavones cause greater bone density, greater bone mechanical strength, and reduced calcium in the urine. It is believed that soy and its isofiavones cause more calcium to be absorbed by the body and bone calcium absorption to be enhanced. Soy isofiavones have estrogenic effects, which are mediated through estrogen receptors. In general, the soy isofiavones are weaker than estradiol and diethylstilbestrol. Most notably, genistein is known to be an estrogen analog and will bind to estrogen receptors with the affinity of 0.2% of estradiol, the major circulating estrogen (Erdman JW, Potter SM. Soy and bone health. The Soy Connection volume 5, 1997). In some instances, the isofiavones have antiestrogenic effects rather than estrogenic effects. It usually depends upon the particular tissue how the isofiavones behaves. In the case of bone, isofiavones have estrogenic action or are estrogen agonists and should improve bone health.
Sixty-six postmenopausal, hypercholesterolemic women were randomized to the NCEP Step i diet (National Cholesterol Education Program) and isolated soy protein with moderate isofiavones, soy protein with high amounts of isofiavones, or casein (control) (Erdman JW, Potter SM. Soy and bone health. The Soy Connection. 1997; volume 5, page 1). The test period lasted 24 weeks. Bone mineral measurements of the lumbar spine, the proximal femur, and the total body were measured by DEXA (dual-energy X-ray absorptionmetry) at the beginning of the study and at the end (24 weeks). Only the lumbar spine bone mineral content and density increased (2%) in the high isofiavones group, and there were no changes in the other groups. The spine is more sensitive to estrogen due to its higher content of trabecular bone. This type of bone undergoes remodeling at a much more rapid rate than the hip, which contains a higher proportion of cortical bone. The 2% increase in a short period was impressive.
Later, John Crouse, III, M.D., professor of internal medicine at Wake Forest University evaluated the effect of soy protein containing different amounts of isofiavones on serum cholesterol and LDL-C levels in mildly hypercholesterolemic patients (American Heart Association, 38th Annual Meeting of Cardiovascular Disease, Epidemiology, and Prevention, March 20, 1998). Subjects had mean cholesterol levels of 241 mg/dL and LDL-C of 164 mg/dL and included men (94), pre-menopausal women (24), and post-menopausual women (38). Subjects received 25 g of soy protein with 4, 25, 42, or 58 mg of the isofiavones. The higher the concentration of the isofiavones administered, the greater the reduction in both total cholesterol and LDL-C. These patients had a 10% reduction in both values after 9 weeks. This is the first report demonstrating that the isofiavones and not the soy protein have the lipid-lowering effect. Soy protein is proposed to lower serum cholesterol by lowering LDL-C through enhanced degradation by small peptides formed during digestion of soy protein. In addition, the soy isofiavones, genistein and daidzein are antioxidants and can cause a significant inhibition of oxidation of LDL. These isofiavones appear to exert this effect on the LDL-C in an aqueous medium inside the arterial wall rather than on LDL-C in the plasma. The isoflavone, genistein, is a specific inhibitor of tyrosine kinase, an enzyme important in the mechanism leading to platelet aggregation and blood clotting. Ingestion of this isoflavone or soy protein may help to decrease thrombosis and prevent mortality from cardiovascular disease (Kurowska EM. Soy and reduced risk of cardiovascular disease. The Soy Connection, vol. 5, page 1, 1997).
Soy may also prevent breast cancer and hot flashes that occur during menopause. Genistein and diadzein have been shown to inhibit human breast cancer and prostate cancer cell lines in cultures by mechanisms independent of steroid binding (ADM, Technical Report, 1998). Isofiavones may exert their effect by inhibiting tumor growth and inducing cell maturation. Chinese women who are pre- menopausal have a reduced incidence of breast cancer compared to women in other cultures where soy is not consumed regularly. This phenomenon has been shown to be true for women in Australia who eat a high soy diet and women in other parts of Southeast Asia.
Women undergoing menopause may have fewer and less severe hot flashes (Barnes S., Kim H., Soy isoflavone, estrogens, and growth factor signaling. The Soy Connection volume 6, 1998). The weak estrogenic effects of isofiavones from soy may help relieve symptoms. Hot flashes decreased by 45% after 12 weeks of 60 g of soy powder (40 g protein) in Italian women.
Based upon the foregoing, phytoestrogen levels of from about 1 to about 100 mg per day, preferably from about 20 to about 60 mg per day, and most preferably about 50 mg per day, provide women with phytoestrogen levels that are physiologically effective and may be used to supplement women's micronutrient needs during post-menopause. The phytoestrogen can be selected from the group consisting of genistin, glycitin, diadzin, genistein, glycitein, diadzein and combinations thereof. A preferred mixture of phytoestrogen may be obtained commercially such as Novasoy (genistein: daidzein: glycitein in a ratio of 1.1 : 1 :0.2) from Archer Daniels Midland (ADM). DIETARY FIBER
Dietary fiber suitable for reducing total serum cholesterol and low density lipoprotein cholesterol is also incorporated in the dietary supplement of the present invention. The dietary fiber can be any soluble fiber (e.g., derived from yeast or plant, such as oat and barley) that ferments in the colon. Examples of suitable dietary fiber, include but are not limited to, nondigestible polysaccharides, plant cell walls, carageenans, mucilages, glucans (e.g., β-glucans), gums, agar, some hemicelluloses, psyllium and pectin. Alternatively, the dietary fiber can be a β- glucan which is soluble in part and insoluble in part, such as whole yeast glucan particles which are most preferred. Yeast β-glucan has been shown to reduce serum cholesterol and LDL-C concentrations and raise high density lipoprotein cholesterol levels. See U.S. Patent No. 4,962,094; the entire teachings of which are incorporated herein by reference. Hypercholesterolemic subjects (> 240 mg/dL) were enrolled in a twelve week study after a three week wash-in period. Subjects received 15 grams of yeast β-glucan (Fibercel™, Alpha-Beta Technology, Inc.; whole yeast glucan particles having an in vivo glucan morphology ) in orange juice for eight weeks. This was followed by a four week period without fiber supplementation. The total cholesterol levels were significantly lower at week seven (approximately 9%, p = 0.05) and at week eight (approximately 7%>, p = 0.05). These levels returned to normal after four weeks without the fiber. The LDL-C was reduced at week six (approximately 7%, p < 0.05) and remained significantly lower than baseline throughout the fiber supplementation. It normalized after four weeks without the fiber. The HDL-C rose significantly after eight weeks of supplementation (15%, p < 0.05) and remained significantly higher even after four weeks without fiber supplementation (p = 0.02). The fiber was well tolerated and patients remained weight stable, indicating that the changes in serum lipids were not attributable to weight loss.
The amount of dietary fiber included in the dietary supplement of this invention will vary depending upon the source and type of fiber incorporated therein, but in any event, should be an amount sufficient to reduce total serum cholesterol and low density lipoprotein cholesterol. Dietary fiber can be incorporated into the dietary supplement in amounts of from about 1 g to about 50 gm day; with preferably from about 5 g to about 20 gm/day; most preferably 15 gm day. A particularly preferred dietary is yeast β-glucan, such as that described in U.S. Patent No. 4,962,094 (Fibercel™). B VITAMINS AND FOLATE
Vitamin B12 (cyanocobalamin), vitamin B6 (pyridoxine) and folic acid are included in the dietary supplement of this invention. These elements act synergistically to reduce serum homocysteine; high levels of which are associated with coronary heart disease. Am. J. Clin. Nutr., 1992, 55:131-138; New Eng. J. Med., 1992, 32:1832-1835; Am i Clin. Nutr., 1989, 50:353-358. The amount of vitamin B12 is from about 1 to about 2,000 mg/day, preferably from about 1.5 to about 4.0 μg/day, with 2.0 μg/day being optimal. The amount of vitamin B6 present in the dietary supplement is from about 1 to about 100 mg/day, preferably from about 1.6 to about 4.6 mg/day, with 4.6 mg/day being most preferred (RDA = 1.6 mg). Folic acid is provided in the dietary supplement as it has been shown to have beneficial cardiac effects and to decrease the risk of cervical dysplasia. Scand. J. Clin. Lab Invest., 1988, 48:215-221. The amount of folate present in the dietary supplement is from about 1 to about 1,000 μg/day, preferably from about 80 to about 800 μg/day, and most preferably about 696 μg/day (RDA = 180 μg). It is desirable to incorporate at least two times RDA amounts of B6 and folate into the dietary supplement of this invention.
Recently, Rimm et al reported that folate and B6 should be ingested in excess of the Recommended Dietary Allowance to prevent coronary heart disease (CHD) in women (JAMA, 279:359-364, 1998). The study included 80,082 women followed over a 14-year period during which time 281 cases of fatal heart attacks occurred. The risk of CHD was reduced among women who regularly used multiple vitamins, the major source of folate and B6 (RR=0.76; 95% CI, 0.65-0.90). The relative risk of developing cardiovascular disease between the highest and lowest quintile for folate and vitamin B6 was 0.55. The best results were seen in women who took 696 μg per day of folate and 131 mg per day of B6.
FORMULATION AND UTILITY OF DIETARY SUPPLEMENTS
The dietary supplements of the invention are intended to be orally administered daily. Preferably, they are formulated for single daily administration, but may be formulated in multiple portions or as time release compositions for more or less frequent administration; for example, the dietary supplement may be formulated as two tablets for twice daily administration. For reasons of size (ease of swallowing) or improved bioabsorption or utilization (e.g., before or after a meal or before sleep), a given dosage may be divided into two, three, or more tablets (or capsules, etc.). A daily dosage may be administered as one tablet, as two tablets taken together, or as two tablets taken separately (e.g., one in the morning and one in the evening). The recommended daily amounts of each ingredient, as described above, serve as a guideline for formulating the dietaiy supplements of this invention. The actual amount of each ingredient per unit dosage will depend upon the number of units daily administered to the post-menopausal woman. This is a matter of product design and is well within the skill of the dietary supplement formulator. The dietary supplements of the present invention may be formulated using any pharmaceutically acceptable forms of the vitamins, minerals and other nutrients discussed above, including their salts. They may be formulated into capsules, tablets, powders, suspensions, gels or liquids optionally comprising a physiologically acceptable carrier, such as but not limited to water, milk, juice, starch, vegetable oils, salt solutions, hydro xym ethyl cellulose, carbohydrate. The dietary supplements may be formulated as powders, for example, for mixing with consumable liquids, such as milk, juice, water or consumable gels or syrups for mixing into other dietary liquids or foods. The dietary supplements of this invention may be formulated with other foods or liquids to provide premeasured supplemental foods, such as single servings bars, for example.
The dietary supplement can be made in a variety of forms, such as baked goods, (e.g., cookies, brownies, fudge, cake, breads, biscuits, crackers,), puddings, confections, (i.e., candy), snack foods (e.g., pretzels, chips), dietary beverages, ice cream, frozen confections and novelties, or non-baked, extruded food products such as bars. The preferred form is a non-baked extruded nutritional bar.
The dietary supplement can also contain other ingredients such as one or a combination of other vitamins, minerals, antioxidants, fiber and other dietary supplements. Selection of one or several of these ingredients is a matter of formulation design, consumer and end-user preference . The amount of these ingredients added to the dietary supplements of this invention are readily known to the skilled artisan and guidance to such amounts can be provided by the U.S. RDA doses for children and adults. Vitamins and minerals that can be added include, but are not limited to, calcium phosphate or acetate, tribasic; potassium phosphate, dibasic; magnesium sulfate or oxide; salt (sodium chloride); potassium chloride or acetate; ascorbic acid; ferric orthophosphate; niacinamide; zinc sulfate or oxide; calcium pantothenate; copper gluconate; riboflavin; beta-carotene; pyridoxine hydrochloride; thiamin mononitrate; folic acid; biotin; chromium chloride or picolonate; potassium iodide; sodium selenate; sodium molybdate; phylloquinone; Vitamin D3; cyanocobalamin; sodium selenite; copper sulfate; Vitamin A; Vitamin E; vitamin B6 and hydrochloride thereof; Vitamin C; inositol; Vitamin B12; potassium iodide.
The dietary supplement can comprise one or a combination of antioxidants in therapeutic amounts. Antioxidants suitable for use in this invention include but are not limited to, vitamin, A, vitamin C, vitamin E, β-carotene, zinc, chromium, selenium and herbs, such as ginkgo biloba, ginseing. The amount of antioxidant(s) per unit serving are a matter of design and will depend upon the total number of unit servings of the dietary supplement daily administered to the patient. The total amount of antioxidant(s) will also depend, in part, upon the condition of the patient. Preferably the amount of antioxidant(s) will be a fraction or multiplier of the RDA amounts. For example, the dietary supplement will comprise 50% RDA antioxidants per unit dosage and the patient will consume two units per day.
Flavors, coloring agents, spices, nuts and the like can be incorporated into the product. Flavorings can be in the form of flavored extracts, volatile oils, chocolate flavorings, peanut butter flavoring, cookie crumbs, crisp rice, vanilla or any commercially available flavoring. Examples of useful flavorings include but are not limited to pure anise extract, imitation banana extract, imitation cherry extract, chocolate extract, pure lemon extract, pure orange extract, pure peppermint extract, imitation pineapple extract, imitation rum extract, imitation strawberry extract, or pure vanilla extract; or volatile oils, such as balm oil, bay oil, bergamot oil, cedarwood oil, cherry oil, walnut oil, cinnamon oil, clove oil, or peppermint oil; peanut butter, chocolate flavoring, vanilla cookie crumb, butterscotch or toffee. In a preferred embodiment, the dietary supplement contains cocoa ro chocolate. Emulsifiers may be added for stability of the final product. Examples of suitable emulsifiers include, but are not limited to, lecithin (e.g., from egg or soy), and/or mono- and di-glycerides. Other emulsifiers are readily apparent to the skilled artisan and selection of suitable emulsifier(s) will depend, in part, upon the formulation and final product. Preservatives may also be added to the dietary supplement to extend product shelf life. Preferably, preservatives such as potassium sorbate, sodium sorbate, potassium benzoate, sodium benzoate or calcium disodium EDTA are used.
In addition to the carbohydrates described above, the dietary supplement can contain artificial sweeteners, e.g., saccharides, cyclamates, aspartamine, aspartame, acesulfame K, and/or sorbitol. Such artificial sweeteners can be desirable if the dietary supplement is intended for an overweight or obese individual, or an individual with type II diabetes who is prone to hyperglycemia.
To manufacture such a food bar, the liquid ingredients are cooked; the dry ingredients are added with the liquid ingredients in a mixer and mixed until the dough phase is reached; the dough is put into an extruded, and extruded; the extruded dough is cut into appropriate lengths; and the product is cooled. For manufacture of other foods or beverages, the ingredients comprising the dietary supplement of this invention can be added to traditional formulations or they can be used to replace traditional ingredients. Those skilled in food formulating will be able to design appropriate foods/beverages with the objective of this invention in mind.
While this invention has been particularly shown and described with references to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.

Claims

CLAIMSWhat is claimed is:
1. A dietary supplement for post-menopausal women or women lacking their ovaries, comprising: calcium, phytoestrogen and vitamin D, present in amounts sufficient to minimize bone loss; dietary fiber, vitamin B6, vitamin B12 and folic acid, present in amounts sufficient to reduce total serum cholesterol and low density lipoprotein cholesterol; and an optional physiologically acceptable vehicle.
2. The dietary supplement of Claim 1 wherein the dietary fiber is ╬▓-glucan is from barley, oat or yeast.
3. The dietary supplement of Claim 1 wherein the phytoestrogen is a soy- derived phytoestrogen.
4. The dietary supplement of Claim 1 wherein the phytoestrogen is an isoflavone.
5. The dietary supplement of Claim 1 wherein the isoflavone is selected from the group consisting of genistein, daidzein, glycitein, genistin, glycitin, diadzin and combinations thereof.
6. The dietary supplement of Claim 1 wherein the isoflavone is a combination of genistein, diadzein and glycitein.
7. The dietary supplement of Claim 1 wherein the calcium is derived from calcium carbonate, calcium citrate, calcium phosphate, calcium maleate, calcium lactate maleate, calcium lactate gluconate, or a combination thereof.
8. The dietary supplement of Claim 1 wherein said supplement is formulated in tablet, powder, suspension, liquid, capsule or gel form, or dietary bar.
9. The dietary supplement, wherein said supplement is formulated into a plurality of oral dosage forms for ingestion on a daily basis.
10. A dietary supplement for post-menopausal women or women lacking their ovaries, the dietary supplement formulated in single or multiple units sufficient to provide a daily dosage of from about 1 mg to about 2000 mg calcium per day; from about 1 ╬╝g to about 20 ╬╝g vitamin D per day; from about 1 mg to about 100 mg isoflavone per day; from about 1 g to about 50 g ╬▓-glucan per day; from about 1 ╬╝g to about 2000 ╬╝g vitamin B12 per day; from about 1 mg to about 100 mg vitamin B6 per day; and from about 1 ╬╝g to about 1000 ╬╝g folic acid per day.
11. A dietary supplement for post-menopausal women or women lacking their ovaries, the dietary supplement formulated in single or multiple units sufficient to provide a daily dosage of from about 500 mg to about 1500 mg calcium per day; from about 5 ╬╝g to about 13 ╬╝g vitamin D per day; from about 20 mg to about 60 mg isoflavone per day; from about 1.5 ╬╝g to about 4.0 ╬╝g vitamin B, 2 per day; from about 1.6 mg to about 4.6 mg vitamin B6 per day; and from about 180 ╬╝g to about 800 ╬╝g folic acid per day.
12. A dietary food bar for post-menopausal women or women lacking their ovaries, comprising: calcium, phytoestrogen and vitamin D, present in amounts sufficient to minimize bone loss; dietary fiber ,vitamin B6, vitamin B12 and folic acid, present in amounts sufficient to reduce total serum cholesterol and low density lipoprotein cholesterol; and an optional physiologically acceptable vehicle.
13. The dietary food bar of Claim 12 wherein the food bar is formulated into a single or multiple units to provide a daily dosage of from about 1 mg to about 2000 mg calcium per day; from about 1 ╬╝g to about 20 ╬╝g vitamin D per day; from about 1 mg to about 100 mg isoflavone per day; from about 1 g to about 50 g ╬▓-glucan per day; from about 1 ╬╝g to about 2000 ╬╝g vitamin B12 per day; from about 1 mg to about 100 mg vitamin B6 per day; and from about 1 ╬╝g to about 1000 ╬╝g folic acid per day.
14. The dietary food bar of Claim 13 wherein the food bar is formulated into a single or multiple units to provide a daily dosage of from about 500 mg to about 1500 mg calcium per day; from about 5 ╬╝g to about 13 ╬╝g vitamin D per day; from about 20 mg to about 60 mg isoflavone per day; from about 1.5 ╬╝g to about 4.0 ╬╝g vitamin B12 per day; from about 1.6 mg to about 4.6 mg vitamin B6 per day; and from about 180 ╬╝g to about 800 ╬╝g folic acid per day.
15. The dietary food bar of Claim 12 wherein the phytoestrogen is a soy-derived phytoestrogen.
16. The dietary food bar of Claim 12 wherein the phytoestrogen is an isoflavone.
17. The dietary food bar of Claim 12 wherein the isoflavone is selected from the group consisting of genistein, daidzein, glycitein, genistin, glycitin, diadzin and combinations thereof.
18. The dietary food bar of Claim 12 wherein the isoflavone is a combination of genistein, diadzein and glycitein.
19. The dietary food bar of Claim 12 wherein the dietary supplement is formulated into a plurality of oral dosage forms for ingestion on a daily basis.
20. A method for daily supplementing micronutrients needs of a post- menopausal woman or a woman lacking ovaries, comprising daily administering to the woman a dietary supplement comprising: calcium, phytoestrogen and vitamin D, present in amounts sufficient to minimize bone loss; dietary fiber, vitamin B6, vitamin B12 and folic acid, present in amounts sufficient to reduce total serum cholesterol and low density lipoprotein cholesterol; and an optional physiologically acceptable vehicle.
21. A method for reducing the risk of osteoporosis in a post-menopausal woman or a woman lacking ovaries, comprising daily administering to the woman the dietary supplement of Claim 1.
22. A method for preventing or reducing the risk of coronary heart disease in a post-menopausal woman or a woman lacking ovaries, comprising daily administering to the woman the dietary supplement of Claim 1.
23. A method for reducing serum cholesterol and low density lipoprotein cholesterol concentration in a post-menopausal woman or a woman lacking ovaries, comprising daily administering to the woman the dietary supplement of Claim 1.
24. A method for raising high density lipoprotein cholesterol concentrations in a post-menopausal woman or a woman lacking ovaries, comprising daily administering to the woman the dietary supplement of Claim 1.
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Cited By (16)

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WO2000049896A1 (en) * 1999-02-24 2000-08-31 Geza Bruckner Dietary compositions and methods
WO2001070212A2 (en) * 2000-03-23 2001-09-27 Interhealth Nutraceuticals Incorporated Method and composition for preventing or reducing the symptoms of menopause
EP1155699A1 (en) * 2000-05-15 2001-11-21 Laboratorios Biosinética Ltda Pharmaceutical and nutritional compositions comprising phytosterols, folic acid, cyanocobalamine, pyridoxine and alimentary fibers
WO2002076481A1 (en) * 2001-03-26 2002-10-03 Niazi Sarfaraz K Composition and method of use in treating sexual dysfunction using cgmp-specific phosphodiesterase type 5 inhibitors
WO2003011263A2 (en) * 2001-07-20 2003-02-13 S.K. Enterprise Gmbh Use of a lactate salt for the treatment and prophylaxis of atherosclerosis
WO2003070255A1 (en) * 2002-02-21 2003-08-28 Schering Aktiengesellschaft Pharmaceutical compositions comprising one or more steroids one or more tetrahydrofolate components and vitamin b12
EP1514540A1 (en) * 2002-05-01 2005-03-16 Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo Calcium-containing tissue strengthening agents and use thereof
DE102005022953A1 (en) * 2005-05-19 2006-11-23 Chemische Fabrik Budenheim Kg Dietary supplements
WO2007100671A2 (en) 2006-02-28 2007-09-07 Nestec S.A. Compositions and methods for inducing bone growth and inhibiting bone loss
WO2008057738A1 (en) * 2006-10-27 2008-05-15 Sciele Pharma, Inc. Isoflavone-containing compositions for the treatment of osteoporosis and inflammatory joint disease
US7687485B2 (en) 1999-09-30 2010-03-30 Drug Tech Corporation Formulation for menopausal women
US20100139524A1 (en) * 2008-12-10 2010-06-10 Taipei Medical University Novel amorphous metal salt for facilitating the handling property of portland cements and dental applications thereof
ES2343294A1 (en) * 2008-10-22 2010-07-27 Farmalider, S.A. Pharmaceutical composition in solid form containing isoflavones, a salt of calcium and vitamin d3 (Machine-translation by Google Translate, not legally binding)
CN103082297A (en) * 2013-02-05 2013-05-08 山西振东五和健康食品股份有限公司 Bone mineral density increase and joint healthcare food and its preparation method
US9216160B2 (en) 2011-10-05 2015-12-22 Jeffrey M. Golini Choline composition
ITUB20153328A1 (en) * 2015-09-01 2017-03-01 Akademy Pharma S R L NUTRACEUTICAL COMPOUND AGAINST THE SYMPTOMS OF THE MENOPAUSE

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US6359017B1 (en) 1999-02-24 2002-03-19 Geza Bruckner Dietary compositions and methods
WO2000049896A1 (en) * 1999-02-24 2000-08-31 Geza Bruckner Dietary compositions and methods
US7687485B2 (en) 1999-09-30 2010-03-30 Drug Tech Corporation Formulation for menopausal women
WO2001070212A2 (en) * 2000-03-23 2001-09-27 Interhealth Nutraceuticals Incorporated Method and composition for preventing or reducing the symptoms of menopause
WO2001070212A3 (en) * 2000-03-23 2002-05-23 Interhealth Nutraceuticals Inc Method and composition for preventing or reducing the symptoms of menopause
EP1155699A1 (en) * 2000-05-15 2001-11-21 Laboratorios Biosinética Ltda Pharmaceutical and nutritional compositions comprising phytosterols, folic acid, cyanocobalamine, pyridoxine and alimentary fibers
WO2002076481A1 (en) * 2001-03-26 2002-10-03 Niazi Sarfaraz K Composition and method of use in treating sexual dysfunction using cgmp-specific phosphodiesterase type 5 inhibitors
US7358277B2 (en) 2001-07-20 2008-04-15 S.K. Enterprise Gmbh Use of a lactate salt for the treatment and prophylaxis of atherosclerosis
WO2003011263A2 (en) * 2001-07-20 2003-02-13 S.K. Enterprise Gmbh Use of a lactate salt for the treatment and prophylaxis of atherosclerosis
WO2003011263A3 (en) * 2001-07-20 2003-12-18 S K Entpr Gmbh Use of a lactate salt for the treatment and prophylaxis of atherosclerosis
WO2003070255A1 (en) * 2002-02-21 2003-08-28 Schering Aktiengesellschaft Pharmaceutical compositions comprising one or more steroids one or more tetrahydrofolate components and vitamin b12
EA007599B1 (en) * 2002-02-21 2006-12-29 Шеринг Акциенгезельшафт Pharmaceutical compositions comprising one or more steroids one or more tetrahydropolate components and vitamin b
AU2002343249B2 (en) * 2002-02-21 2009-02-05 Bayer Schering Pharma Aktiengesellschaft Pharmaceutical compositions comprising one or more steroids one or more tetrahydrofolate components and vitamin B12
US8778882B2 (en) 2002-05-01 2014-07-15 Hayashibara Co., Ltd. Agent for strengthening calcium containing tissue and use thereof
EP1514540A4 (en) * 2002-05-01 2006-03-08 Hayashibara Biochem Lab Calcium-containing tissue strengthening agents and use thereof
EP1514540A1 (en) * 2002-05-01 2005-03-16 Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo Calcium-containing tissue strengthening agents and use thereof
DE102005022953A1 (en) * 2005-05-19 2006-11-23 Chemische Fabrik Budenheim Kg Dietary supplements
WO2007100671A2 (en) 2006-02-28 2007-09-07 Nestec S.A. Compositions and methods for inducing bone growth and inhibiting bone loss
EP1988891A2 (en) * 2006-02-28 2008-11-12 Nestec S.A. Compositions and methods for inducing bone growth and inhibiting bone loss
EP1988891A4 (en) * 2006-02-28 2011-06-22 Nestec Sa Compositions and methods for inducing bone growth and inhibiting bone loss
US8242100B2 (en) 2006-02-28 2012-08-14 Nestec Sa Compositions and methods for inducing bone growth and inhibiting bone loss
WO2008057738A1 (en) * 2006-10-27 2008-05-15 Sciele Pharma, Inc. Isoflavone-containing compositions for the treatment of osteoporosis and inflammatory joint disease
ES2343294A1 (en) * 2008-10-22 2010-07-27 Farmalider, S.A. Pharmaceutical composition in solid form containing isoflavones, a salt of calcium and vitamin d3 (Machine-translation by Google Translate, not legally binding)
US20100139524A1 (en) * 2008-12-10 2010-06-10 Taipei Medical University Novel amorphous metal salt for facilitating the handling property of portland cements and dental applications thereof
US8298328B2 (en) * 2008-12-10 2012-10-30 Taipei Medical University Amorphous metal salt for facilitating the handling property of portland cements and dental applications thereof
US9216160B2 (en) 2011-10-05 2015-12-22 Jeffrey M. Golini Choline composition
CN103082297A (en) * 2013-02-05 2013-05-08 山西振东五和健康食品股份有限公司 Bone mineral density increase and joint healthcare food and its preparation method
ITUB20153328A1 (en) * 2015-09-01 2017-03-01 Akademy Pharma S R L NUTRACEUTICAL COMPOUND AGAINST THE SYMPTOMS OF THE MENOPAUSE
EP3138562A1 (en) * 2015-09-01 2017-03-08 Akademy Pharma S.r.l. Nutraceutical compound against menopausal symptoms

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