Vitamin and mineral supplements for human and veterinary use are commonplace. Some diets, heavy physical exercise and disease conditions may require the intake of considerable quantities of minerals apart from those generally obtained through what otherwise would be considered a normal diet. Calcium and trace mineral supplementation is important primarily for those who have inadequate diets, including growing children. Older adults have an additional need for calcium to help prevent the bone loss which occurs as a normal consequence of the aging process. In particular, postmenopausal women need additional calcium due to hormonal changes which can accelerate the bone loss rate leading to a further diminishment in bone mass.
The trace minerals which affect bone growth are copper, zinc and manganese. Supplementation of the diet with these minerals along with a highly bioavailable source of calcium is highly desirable. Commercially available mineral supplements are useful in many circumstances where increased mineral intake is desirable. Most of these multi-vitamin and multi-mineral tablets are low in calcium, requiring separate supplementation with calcium sources. In addition, not all calcium sources are equal in terms of bioavailability and absorption. It would be more convenient if all of the minerals could be administered conjointly in a convenient and/or pleasant tasting form which would not require extra attention, planning and implementation by the user. This could be done in the form of foods and beverages as well as in the form of tablets.
There are well-recognized problems associated with adding both mineral and calcium supplements to foods and beverages. Some of these are taste; calcium tends to be chalky in flavor. In addition, the solubility of many calcium sources prevents them from being added to many beverages. Others are interactions of the minerals with the food or beverage which affects the stability and/or the bioavailabilty of the product. This invention provides a means for making such product.
This invention also relates to methods of building bone in humans and other animals, i.e., for the treatment of age-related bone loss and related disorders. In particular, this invention relates to such methods of treatment by administration of certain calcium salts and the minerals, copper, zinc and manganese.
Calcium is the fifth most abundant element in the human body. It plays an important role in many physiological processes, including nerve and muscle functions. Not surprisingly, nutritional and metabolic deficiencies of calcium can have broad-ranging adverse effects. Since about 98% to 99% of the body's calcium is found in bone tissues, many of these adverse effects are manifested through deficiencies in the structure, function and integrity of the skeletal system.
The most common metabolic bone disorder is osteoporosis. Osteoporosis can be generally defined as the reduction in the quantity of bone, either from the reduction in bone formation or the acceleration of bone resorption, in either event the result is a decrease in the amount of skeletal tissue. In general, there are two types of osteoporosis: primary and secondary. "Secondary osteoporosis" is the result of an identifiable disease process or agent. However, approximately 90% of all osteoporosis cases are idiopathic "primary osteoporosis". Such primary osteoporosis includes postmenopausal osteoporosis, age-associated osteoporosis (affecting a majority of individuals over the age of 70 to 80), and idiopathic osteoporosis affecting middle-aged and younger men and women.
For some osteoporotic individuals the loss of bone tissue is sufficiently great so as to cause mechanical failure of the bone structure. Bone fractures often occur, for example, in the wrist, hip and spine of women suffering from postmenopausal osteoporosis. Kyphosis (abnormally increased curvature of the thoracic spine) may also result.
The mechanism of bone loss in osteoporotics is believed to involve an imbalance in the process of "bone remodeling". Bone remodeling occurs throughout life, renewing the skeleton and maintaining the strength of bone. Two reactions are involved, bone loss or resorption and bone growth or accretion. This remodeling occurs in a series of discrete pockets of activity in the bone, called "osteoclasts" and "osteoblasts". Osteoclasts (bone dissolving or resorbing cells) are responsible for the resorption of a portion of bone within the bone matrix, during the resorption process. After resorption, the osteoclasts are followed by the appearance of osteoblasts (bone forming cells), which then refill the resorbed portion with new bone.
In young healthy adults, the rate at which the osteoclasts and osteoblasts are formed maintains a balance of bone resorption and bone formation. However, as normal consequency of aging an imbalance in this remodeling process develops, resulting in loss of bone at a rate faster than the accretion of bone. As imbalance continues over time the reduction in bone mass and thus bone strength leads to fractures.
Many compositions and methods are described in the medical literature for the "treatment" of osteoporosis. See, for example, R. C. Haynes, Jr. et al., "Agents affecting Calcification", The Pharmacological Basis of Therapeutics, 7th Edition (A. G. Gilman, L. S. Goodman et al., Editors, 1985); and G. D. Whedon et al., "An Analysis of Current Concepts and Research Interest in Osteoporosis", Current Advances in Skeletogenesis (A. Ornoy et al., Editors, 1985). Estrogen is often used to affect the metabolism of calcium by influencing the osteoblast cells. Treatments using fluoride have also been described. However, the utility of such agents may be limited, because of possible adverse side effects. See W. A. Peck, et al., Physician's Resource Manual on Osteoporosis (1987), published by the National Osteoporosis Foundation.
Nutritional therapies for osteoporosis have also been proposed. Many calcium-containing compounds and compositions have been described for use as nutritional supplements. Many commercial preparations are also available, typically containing calcium carbonate or calcium phosphate. Other calcium salts have also been described for use in calcium supplements, including calcium lactate, calcium citrate and calcium gluconate.
U.S. Pat. No. 3,949,098 issued Bangert (assigned Nabisco, 1976) describes a nutritious orange drink concentrate that contains whey protein. The patent suggests the addition of minor amounts of vitamins and other nutrients which include various cupric salts, manganese salts, zinc salts, as well as calcium salts.
German OLS 2,845,570 issued to E.R.E. (Europe Representation Establishment, 1980) describes a honey containing composition. Honey contains low levels of calcium, manganese, copper as well as trace amounts of magnesium, iron, phosphorous, silicon and nickel. The value of honey as a medicant is undisputed according to this patent application. This application claims a honey containing composition with levarotatory ascorbic acid and citric acid. This patent has issued as U.S. Pat. No. 4,243,794 (1981).
U.S. Pat. No. 4,497,800 issued to Larsen et al (assigned Mead Johnson & Company, 1985) describes a nutritionally complete ready-to-use liquid diet for providing total patient nourishment. The diet contains free amino acids and small peptides, a carbohydrate source, and nutritionally significant amounts of all essential vitamins and minerals, and stabilizers. The minerals include calcium, copper, zinc and manganese, among others. Most of these minerals are given as the gluconate salt.
"Effects of calcium carbonate in hydroxyapatite on zinc and iron retention in postmenopausal women", Dawson-Hughes, Seligson and Hughes, American Journal of Clinical Nutrition, 44, 83-88 (1986) describes the effect of calcium carbonate on whole-body retention of zinc and iron in thirteen healthy post menopausal women. The test meal, including both dry food and a formulated beverage, included calcium, copper and zinc at a level of one-third the usual daily requirement. These are levels normally found in human diets.
U.S. Pat. No. 3,992,555 issued to Kovacs (assigned Vitamins, Inc., 1976) describes food supplements prepared by mixing assimilable iron compounds, vitamins and minerals with a heated edible fat carrier. The minerals include calcium, zinc, copper, and manganese among others.
U.S. Pat. No. 3,950,547 issued to Lamar et al (assigned Syntex Inc, 1976) describes a dietary composition containing peptides and/or amino acids, lipids and carbohydrates in an aqueous emulsion. Suitable minerals for adding at low levels include among others calcium, copper and zinc.
U.S. Pat. No. 4,107,346 issued to Kravitz (1978) describes a dietary salt composition for use as a replacement for salt in foods. The role of copper is described as a component of several enzymes essential for nutrition. The patent further discloses that "spontaneous fractures are common in animals feeding off copper deficient soils or who are given artificially depleted copper diets". (column 4, lines 20-30) Zinc is described as helping in growth, wound healing and improving taste and smell. Clinical symptoms of manganese deficiency have not been observed in man. However, there is no question that manganese is essential for human nutrition. Main manifestations of its deficiency are impaired growth and skeletal abnormalities. Calcium is described as being necessary for blood coagulation, for calcium retention, and for relieving the symptoms of osteoporosis. Examples of salts that contain these four trace minerals are disclosed.
U.S. Pat. No. 4,070,488 issued to Davis (unassigned, 1978) discloses a highly stabilized balanced nutritive composition useful in supplementing the diet of humans and/or animals. This composition contains gelatin. The patent discloses that the sulfhydryl groups of the gelatin can render copper inactive toward ascorbic acid.
U.S. Pat. No. 4,214,996 issued to Buddemeyer et al (R.G.B. Laboratories, 1980) discloses mineral compositions which are very soluble. These compositions contain calcium, phosphorus, zinc, as well as manganese. Not all of the compositions that are described contain all four elements.
U.S. Pat. No. 4,351,735 to Buddemeyer et al (R.G.B. Laboratories, 1982) is related to the '996 patent.
"Nutrients and Nutrition of Citrus Fruits," Citrus Nutrition and Quality, Ting, (American Chemical Society, 1980) discloses the presence of certain trace minerals in orange juice. These include copper, zinc, iron and manganese. Calcium and magnesium are the two major divalent cations in orange juice. The levels of all the minerals are low.
Hungerford et al, "Interaction of pH and ascorbate in intestinal iron absorption," (1983) describes the iron absorption from various food materials. The diet which was low in iron also contained calcium carbonate, manganese sulfate and copper sulfate among others.
U.S. Pat. No. 4,419,369 issued to Nichols et al (assigned Baylor College of Medicine, 1983) describes an improved dietary protein mineral module for infants. An approximate analysis of the material shows the presence of iron, zinc, copper and calcium.
The utility of these known supplements varies. Unlike agents (such as estrogen) which affect the metabolism of bone, calcium nutritional supplements have been thought to merely provide a source for calcium (which may or may not be properly absorbed and metabolized). See, for example, B. Riis et al., "Does Calcium Supplementation Prevent Postmenopausal Bone Loss?," New England J. of Medicine, 316, 173-177 (1987); L. Nilas et al., "Calcium Supplementation and Postmenopausal Bone Loss," British Medical Journal, 289, 1103-1106 (1984); and H. Spencer et al., "NIH Concensus Conference: Osteoporosis," Journal of Nutrition, 116, 316-319 (1986).
It has now been discovered, however, that the administration of mixtures of certain calcium salts, along with trace minerals, copper, zinc and manganese are surprisingly effective for delaying age-related loss of bone. In particular, as compared to nutritional regimens known in the art, these methods afford greater efficacy in the treatment of age-related bone loss and related disorders.
It would be desirable, therefore, to have mixed calcium and mineral supplements which are compatible and nutritionally available. It would also be quite useful to have such supplements which could be added to food and beverage compositions without undesirably affecting organoleptic or aesthetic properties.
It is an object of the present invention to provide calcium mineral supplements which provide bone growth and can be used to treat age-related bone loss or to correct the imbalance that occurs between bone formation and bone resorption.
It is a further object of this invention to provide foodstuffs, beverages and beverage concentrates which are supplemented with calcium and trace minerals.
These and other objects are secured herein, as will be seen from the following disclosure.