Forbones Xtra D Medical Information
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The objective of daily calcium supplementation is to assure adequate calcium intake because inadequate calcium intake can lead to osteoporosis and osteomalacia. While osteomalacia is relatively rare in the U.S., osteoporosis is a significant problem in people over 65 because of the risk of bone fracture. Dairy products are the main source of dietary calcium in the U.S. diet1, but individuals who do not consume sufficient dairy products may be at risk. Efficiency of calcium absorption declines with age, and certain gastrointestinal diseases, surgeries, and drugs may also decrease absorption or increase excretion.
Functions of Calcium and Phosphorus
Calcium and phosphorus have multiple functions throughout the body, although about 99% of body stores of calcium1 and 80% of phosphorus4 are in bone. In the skeleton, calcium and phosphorus (as phosphate) provide most of the mineral content and are responsible for the strength and rigidity of the bony skeleton. Non-skeletal calcium is present in plasma and its concentration is controlled tightly via endocrine control over absorption through the intestines and excretion through the kidneys in urine. Calcium ion (Ca++) is essential to muscle contraction, including cardiac muscle, and for conduction of electrical impulses in the heart. Calcium ion is also involved in neurotransmitter release, cell membrane integrity and blood coagulation.2 Phosphorus is essential to energy transfer within cells and in transferring nutrients and other materials into and out of cells.4
The calcium in the skeleton serves not only as the structural mineral in bone along with phosphate but as a pool available to maintain circulating calcium levels. There is a constant turnover of bone, with old bone being resorbed and new bone deposited. The calcium and phosphorus freed by resorption are available in the circulating pool for deposition as new bone and to fulfill the additional roles of calcium in cell function throughout the body. A portion of circulating calcium is lost daily through excretion via the kidneys and the intestinal tract. Calcium lost from the body must be replaced from diet or supplementation to assure there is adequate calcium present for deposition of new bone. Phosphate, too, must be replaced from diet, although phosphorus is widely distributed in foodstuffs as opposed to calcium, which comes mostly from dairy products in North America.1,2,4
Calcium Absorption and Excretion
Calcium is absorbed through the intestinal tract via two mechanisms. A vitamin D-dependent active transport mechanism operates in the duodenum and proximal jejunum, the part of the small intestine just below the stomach. This area has the highest rate of absorption, about 3 times that of the remainder of the gut.5 A second mechanism for absorption is diffusion, which occurs throughout the small and large intestine.3
The dual absorption mechanism helps compensate for varying amounts of calcium in diet because the efficiency of absorption depends on the amount of calcium consumed. Efficiency of absorption goes down when calcium intake is high and increases when intake is low. Unfortunately, increasing age tends to reduce absorption efficiency.2,5 In addition, certain drugs, such as steroids and phenytoin depress calcium intestinal transport. Diseases, such as inflammatory bowel disease (ulcerative colitis and Crohn’s disease), where fat malabsorption, diarrhea and chronic intestinal inflammation are present increase calcium loss through feces. Surgical procedures for weight reduction that involve bypass of the duodenum may reduce absorption efficiency, since the portion of the intestinal tract with highest absorption efficiency is the duodenum and proximal jejunum. Foods which contain oxalates or phytates can form complexes with calcium that can’t be absorbed.1 Phytates are present in unsprouted seeds, grains and legumes and in raw nuts. Oxalates are present in spinach and seeds.
Calcium is excreted from the body in feces, urine and to a small extent in sweat. During lactation, mothers secrete significant levels of calcium into breast milk. Fecal loss of calcium makes up the bulk of excreted calcium under normal conditions, with the excreted volume made up of unabsorbed dietary calcium and calcium contained in mucosal cell sloughing from the intestinal tract. Urinary calcium excretion accounts for almost all other calcium loss, except, as noted above, during lactation or extensive sweating. Calcium loss in urine is influenced by parathyroid hormone, which regulates reabsorption of calcium in the kidney. Medical conditions affecting parathyroid hormone therefore can impact calcium loss in urine. Some diuretic drugs (“water pills”) can increase calcium loss by partially blocking reabsorption of calcium in the kidney. Corticosteroid drugs such as prednisone, which are often used to treat inflammation, also increase loss of calcium and increase the need for intake of calcium in diet or through supplements.
Role of Vitamin D
The body obtains Vitamin D from diet and through exposure to sunlight. However, various population studies show vitamin D insufficiency persists in North America and Europe, particularly during winter months when sun exposure is reduced. Once absorbed from diet or generated in the skin, vitamin D is converted in the liver to a metabolite, 25 hydroxy vitamin D. This metabolite is inactive, but circulating 25 hydroxy vitamin D is converted in the kidney and possibly other sites to the active metabolite 1,25 dihydroxy vitamin D.6 The level of the 1,25 dihydroxy metabolite is tightly controlled by feedback mechanisms based on calcium levels in blood. As calcium levels in blood increase, conversion of vitamin D to its active metabolite decreases.7
Vitamin D facilitates active absorption of calcium and phosphate in the intestine through the actions of 1,25 dihydroxy vitamin D, which stimulates active calcium uptake by the cells lining the intestine. The mechanism for facilitating absorption involves binding the vitamin D metabolite to the vitamin D receptor in the cells and subsequent opening of the calcium channel in the cell membrane in the intestinal wall, stimulation of the cell calcium binding protein (calbindin), which transports calcium through the cell, and stimulation of the plasma membrane calcium ATPase, which pumps calcium from the cell to the blood stream.7,8
Vitamin D also has a role in maintaining levels of calcium in circulation in the blood through interaction with parathyroid hormone in mobilizing calcium (and phosphate) from bone and reducing excretion in urine through the kidneys.2 Vitamin D stimulates bone cells to form new bone but, at higher levels, increases calcium mobilization from old bone.9
Malabsorption of Vitamin D
Diseases and surgeries of the digestive tract can impair Vitamin D absorption. Since Vitamin D is fat soluble, any disease that interferes with breakdown and digestion of fats can reduce absorption of Vitamin D (and the other fat-soluble vitamins – A, E and K). Some diseases impacting fat absorption are Inflammatory Bowel Disease (Crohn’s disease and ulcerative colitis), cystic fibrosis, chronic pancreatitis, and short bowel syndrome. Certain surgeries for weight reduction, especially bypass surgery, can impair fat absorption and thus Vitamin D absorption.
Forbones contains a water-miscible form of Vitamin D that promotes good absorption. The water-miscible form more easily forms the small particles necessary to pass through the gut wall compared to oily forms of Vitamin D for people with fat malabsorption.
Forms of Calcium
The most frequently found form of calcium in dietary supplements is calcium carbonate. Other forms of calcium used in supplements are calcium citrate, calcium gluconate and calcium phosphate. The carbonate form is the most frequently used because it is inexpensive and not as bulky as some other forms. The principal drawback to carbonate is that it releases carbon dioxide gas on contact with stomach acid and can cause abdominal distension, pain and discomfort. Gluconate and citrate forms of calcium are more bulky, creating problems for making tablets of a size that can be swallowed. For that reason and because they are more water soluble, these forms are more often used in liquid or chewable products. Calcium phosphate does not produce carbon dioxide in stomach acid and can be formed into tablets of reasonable size, making it a good choice where excess gas can be an issue.
1. Weaver CM, Heaney RP, Calcium (Ch 7) in Modern Nutrition in Health and Disease (Shils ME, Olson JA, Shike M, Ross AC, Eds.),Williams & Wilkins, Baltimore 1999:141-155
2. Marcus R, Agents Affecting Calcification and Bone Turnover (Ch 62) in Goodman & Gilman’s Pharmacological Basis of Therapeutics (Hardman JG, Limbird LE, Gilman AG, Eds), McGraw-Hill, New York, 2001:1715-1743
3. Bronner F, Intestinal Calcium Transport: The Cellular Pathway, Miner Electrolyte Metab 1990;16:94-100
4. Knochel JP, Phosphorus (Ch 8) in Modern Nutrition in Health and Disease (Shils ME, Olson JA, Shike M, Ross AC, Eds.),Williams & Wilkins, Baltimore 1999: 157-167
5. Civitelli R, Avioli LV, Calcium, Phosphate and Magnesium Absorption (Ch 65) in Physiology of the Gastrointestinal Tract, 3rd Ed (Johnson LR, ed), Raven Press, NY; 1994: 2173-2181
6. Holick MF, Vitamin D (Ch 18) in Modern Nutrition in Health and Disease (Shils ME, Olson JA, Shike M, Ross AC, Eds.),Williams & Wilkins, Baltimore 1999:329-345
7. Heaney RP, Functional Indices of Vitamin D Status and Ramifications of Vitamin D Deficiency, Am J Clin Nutr;Vol 80, No 6, Dec 2004:1706S-1709S.
8. Merck Manual, 17th Edition Beers MH, Berkow R, eds), Merck Research Laboratories, 1999: 141
9. op. cit., p35