Calcium is the most abundant cation in the human body and comprises about 1.5–2% of the total body weight. The body of healthy humans contains about 1250 g of calcium, about 99% of which is present in bones and teeth as deposits of calcium phosphate and calcium hydroxide. The remaining 1% is found in extracellular fluid, soft tissues, and as a component of various membrane structures.
Food Sources
Calcium is present in significant amounts in only a few foods, with milk and dairy products as the best sources. A quart of milk supplies about 1200 mg of calcium in a readily assimilable form. Broccoli and leafy green vegetables such as turnip greens and kale have appreciable amounts of calcium. Other foods relatively high in calcium salts are beans, TABLE1 Essential Macrominerals in the Adult Human Body and Their Major Functions
Mineral
% of body
weight Totala Function
Calcium 1.78 1250 g Structural component of bones and teeth;
regulation of excitable tissues (nerve and muscle excitability); blood clotting; activation of some enzymes; mediates action of some hormones.
Phosphorus 0.96 670 g Structural component of bones and teeth;
component of nucleic acids, nucleotide coenzymes, ATP, GTP, etc.; essential in intermediary metabolism, enzyme systems;
maintenance of osmotic and acid–base balance.
Magnesium 0.04 25 g Constituent of bones and teeth; nerve impulse transmission; activator of some enzymes;
structural integrity of mitochondrial membranes.
Potassium 0.19 130 g Regulation of nerve and muscle excitability;
regulation of osmotic pressure; acid–base balance, water balance.
Sodium 0.14 100 g Excitability of nerves, muscles, active transport of glucose, regulation osmotic pressure, acid–base balance, water balance.
Chloride 0.15 105 g Component of gastric juice, regulation of osmotic pressure, acid–base balance, water balance.
Sulfur 0.25 175 g Component of thiamin, biotin, pantothenic acid;
lipoic acid, methionine, cysteine, taurine;
stabilizes structures of several proteins.
aAverage amount in adults weighing 70 kg.
shellfish, and fish of the sardine type in which bones are eaten. Some vegetables such as spinach contain appreciable quantities of oxalic acid, which forms insoluble calcium oxalate in the intestinal tract and lessens the absorption and utilization of calcium present.
Absorption
The absorption of calcium is quite variable and depends on a number of factors including various ions, acid–base status, lactose, and vitamin D. Calcium can be precipitated as the phosphate, carbonate, oxalate, phytate, sulfate, or calcium soap in the presence of excess fatty acids. All of these are insoluble and, therefore, poorly absorbed. Calcium salts are more soluble in acid than in basic solutions. Lactose exerts a favorable effect on calcium absorption. The beneficial effect is the result of chelation of calcium by lactose, which forms a soluble complex of low molecular weight. Vitamin D is important in facilitating the absorption of calcium. The active form of vitamin D induces the synthesis of a transport protein for calcium that increases calcium absorption. Calcium from the intestine is absorbed by active transport (i.e., against the concentration gradient by a TABLE2 Essential Trace Minerals in the Human Body and Their Major Functions
Mineral
% of body
weight Totala Functions
Iron 0.006 4 g Structural component of hemoglobin, myoglobin, cytochromes, some enzymes.
Copper 0.0001 80 mg Component of ceruloplasmin (iron mobilization), cytochrome oxidase (energy metabolism), superoxide dismutase (free radical inactivation), lysyl oxidase (cross-linking of elastin), tyrosinase, dopamine hydroxylase.
Zinc 0.003 2 g Component of several enzymes (e.g., alcohol dehydrogenase, carbonic anhydrase, alkaline phosphatase, carboxypeptidase, thymidine kinase); role in wound healing.
Cobalt trace 1.1 mg Component of vitamin B12
Molybdenum 0.00001 9 mg Component of xanthine oxidase, aldehyde oxidase, sulfite oxidase
Selenium 0.00002 15 mg Component of glutathione peroxidase, iodothyronine 5-deiodinase.
Manganese 0.00002 20 mg Component of pyruvate carboxylase; activation of many enzymes; necessary for normal skeletal and connective tissue development.
Iodine 0.00004 30 mg Constituent of thyroxine, triiodothyronine.
Chromium 0.00001 8 mg Component of glucose tolerance factor;
potentiates insulin action; involved in glucose transport into the cell.
Fluorine 0.0015 1 g Structural component of calcium hydroxyapatite of bones and teeth.
Siliconb 0.001 700 mg Apparent role in the formation of connective tissue and bone matrix.
aAverage amount in adults weighing 70 kg.
bHuman requirement for this mineral is not known.
Inorganic Elements (Minerals) 87
process requiring energy). The average person has a high degree of adaptability to high or low amounts of calcium in the diet. Those eating a low calcium diet appear to have more efficient calcium absorption than those consuming a diet high in calcium. Thus, if the intake of calcium is lowered, intestinal efficiency and the ability to absorb and retain calcium increases whereas raising the intake reduces the efficiency of absorption. Under normal conditions, approximately 33% of the ingested calcium is absorbed.
Once calcium is absorbed through the walls of the intestine it is transported in the plasma and released to fluids bathing the tissues of the body. From there, the cells absorb whatever calcium is needed for their normal functioning and growth.
The level of calcium in plasma is maintained at about 10 mg/dl and is regulated by the endocrine system involving parathyroid hormone (PTH), calcitonin, and the active form of vitamin D. Plasma calcium exists in three forms. About 50% of the calcium in the plasma is ionized; it is the only fraction that is physiologically active and is assumed to be the fraction under hormonal control. The other 50% is nonionized and physiologically inert. Forty to 45% is bound to plasma protein and 5–10% is complexed with ions such as citrate, bicarbonate, and phosphate. As the blood plasma is filtered in the kidney about 99% of the calcium (10 g/day) is reabsorbed and the remaining 1% (usually about 100–
175 mg/day) is excreted in the urine.
Functions
Calcium serves as the principal component of the skeleton and provides the strength and rigidity of the skeleton and teeth. It is deposited in bone as calcium phosphate and calcium hydroxide, which make up a physiologically stable compound called hydroxy-apatite, Ca10(PO4)6(OH)2. Because calcium and phosphorus are the predominant ele-ments in these compounds, an adequate supply of both must be present before they can be precipitated from fluids surrounding the bone matrix. Calcification apparently occurs when the product of the level of calcium and phosphorus in the blood and extracellular fluid exceeds 30 (e.g., mg of calcium mg of phosphorus in 100 ml of blood > 30). The skeleton serves as a vital physiological tissue providing a readily available source of calcium and phosphorus for homeostatic control when the absorbance of these nutrients from the intestine is insufficient, or when their excretion from the body is excessive.
The bone tissue is constantly being reshaped (or remodeled) according to various body needs and stresses, with as much as 700 mg of calcium entering and leaving the bones each day.
Cells use their internal calcium ion concentration to regulate a variety of processes.
The calcium ion level is kept low by an ATP-dependent calcium pump; in nerve and muscle, an additional pumping system is also present. In most cells, calcium release from the endoplasmic reticulum by inositol triphosphate triggers the actions, which differ according to cell type. In nerve cells, calcium-gated ion channels are used to start neurotransmitter release. Glycogen breakdown, muscle contraction, and the secretion of small molecules such as insulin by the pancreas or histamine by mast cells are calcium-regulated processes. Calcium is required to initiate the blood clotting process. The ionized calcium stimulates the blood platelet to release thromboplastin, which is a necessary cofactor for the conversion of prothrombin to thrombin. In addition, it mediates the intracellular action of many hormones.
To carry out these various roles, calcium must be available to the appropriate tissue in the proper concentration. This is accomplished by PTH, calcitonin, and the active form of vitamin D by controlling the site of entry of calcium in the circulation (intestinal
absorption) and the site of exit (the kidney). In addition, the large store of calcium in bone is available for deposits or withdrawals depending upon peripheral demands. When the blood calcium level falls, PTH is secreted, which acts to restore calcium to its normal concentration range. PTH stimulates renal tubular calcium absorption and inhibits phosphate reabsorption. This leads to decreased urinary excretion of calcium and increased phosphate excretion. PTH mobilizes bone calcium by direct stimulation of osteoclasts. It also stimulates the conversion of vitamin D to its active form by the kidney. The active form of vitamin D acts on intestinal cells to induce the synthesis of a specific calcium-binding protein that facilitates intestinal calcium absorption. All these actions of PTH increase blood calcium. Calcitonin is secreted when blood calcium levels are elevated. It acts to lower both calcium and phosphorus by inhibiting bone resorption.
Thus, it aids in counterbalancing the action of PTH and maintaining blood calcium at normal level. The active form of vitamin D not only increases intestinal absorption but also promotes bone resorption directly, an apparently paradoxical situation because it is also required for adequate calcification of cartilage and osteoid.
Disorders of Calcium
Calcium deficiency in children can lead to rickets, and in adults to osteomalacia.
These two diseases are associated with vitamin D deficiency or, rarely, with alterations in its metabolism or action. In osteoporosis, the amount of bone is reduced without a change in its chemical composition. This disorder is associated with a variety of factors and a negative calcium balance. Whether deficient dietary intake of calcium is the cause of the disease is not clear. Calcium supplementation and hormones are frequently used in treatment. Potassium bicarbonate to balance the metabolic production of acid is beneficial.
A decrease in ionic plasma calcium is a cause of tetany, a condition marked by severe, intermittent spastic contraction of muscle and by muscular pain. Tetany occurs occasionally in the newborn infant and sometimes in rickets and in fat malabsorption. In the last instance, a loss of vitamin D accounts for diminished calcium absorption, resulting in a plasma calcium level too low to be compensated by the PTH.
Malignancy and primary hyperparathyroidism are the most common causes for hypercalcemia. Hematological malignancies, such as multiple myeloma, tend to be responsible for more hypercalcemia than patients with solid tumors. Because calcium is an important regulator of many cellular functions, hypercalcemia can produce abnormalities in the neurologic, cardiovascular, pulmonary, renal, gastrointestinal, and musculoskeletal systems. The clinical manifestations include muscle weakness, anorexia, thirst, polyuria, and dehydration.
Requirement
The amount of calcium retained by the body depends not only on the amount in the diet but also on the efficiency of absorption and on excretion; hence, it is difficult to set an absolute standard for the calcium requirement. Moreover, the need for calcium appears to be flexible. In certain parts of the world, the adult population gets along well with a diet containing low amounts of calcium.
The calcium requirements are based on balance studies that measure the intake and output of calcium over period of time. The Food and Nutrition Board of The National Academy of Science in its 1989 revision recommends 800 mg/day of calcium for adults.
Inorganic Elements (Minerals) 89
This amount covers the basic needs and allows for a margin of safety. This allowance is on the basis that calcium losses are approximately 320 mg/day. Because only a portion of the dietary calcium is absorbed, 800 mg is suggested for maintaining balance. The RDA for infants up to 1 year old is between 400 and 600 mg. For children 1–10 years old, the allowance is set at 800 mg, and for those between the ages of 11 and 18 the recommended amount is 1200 mg per day. To meet the needs of the growing fetus and the mother during pregnancy, the RDA for calcium during gestation is 1200 mg/day compared with 800 mg for nonpregnant women. Human milk contains 25–35 mg calcium/100 ml. For lactating women this represents an additional 150–200 mg depending on the amount of milk produced, so to meet this demand the RDA during lactation is set at 1200 mg/day.
Toxicity
A number of conditions involving increased bone breakdown or calcium absorption can increase the blood calcium. A very high intake of calcium and the presence of a high intake of vitamin D are a potential cause of hypercalcemia. This may lead to excessive calcification not only in the bone but also in the soft tissues such as the kidneys.
B. Phosphorus
Phosphorus as a primary, secondary, or tertiary ion is present in the body fluids (about 16%
of the total) and as a constituent of bones and teeth (about 84% of the total). Phosphorus constitutes 1% of the human body weight. It is estimated that the adult body contains 12 g phosphorus per kilogram of fat-free tissue or about 670 g in the adult males and 630 g in adult females.
Food Sources
Phosphorus is a major constituent of all plant and animal cells and, therefore, is present in all natural foods. In general, foods rich in protein are also rich in phosphorus. Meat, poultry, fish, eggs, milk, and cereal products are good sources of phosphorus, as they are for calcium.
Absorption
Most of the dietary phosphorus is absorbed as free phosphate, and about 60–70% of our normal intake is absorbed. The most favorable absorption of inorganic phosphate takes place when calcium and phosphorus are ingested in approximately equal amounts.
Because milk has calcium and phosphorus in equal amounts it is a good source of phosphorus. Organic phosphate esters of phytic acid in cereals and seeds are not a source of phosphorus because the human intestinal tract lacks phytase. Phytic acid forms insoluble calcium salts in the intestinal lumen and interferes with calcium absorption.
Available evidence indicates that phytic acid also interferes with the absorption of iron and zinc. The transport of phosphate from the small intestine is an active, energy-dependent process. Like calcium, phosphorus absorption is regulated by the active form of vitamin D. In general, in adults, about two-thirds of the ingested phosphate is absorbed and what is absorbed from the intestine is almost entirely excreted in the urine. In growing children, however, there is a positive balance of phosphate. The serum inorganic phosphate level is maintained closely in the range of 3–4 mg/100 ml in adults. Levels are higher in infants (6 mg/dl) and young children (4.5 mg/dl). The kidneys provide the main excretory route for the regulation of serum phosphate level.
Functions
The addition or removal of phosphate groups of proteins is the main method of regulating metabolism, cell division, and differentiation. Along with calcium, phosphorus has a major role in the formation of bones and teeth. Phosphorus has several other very important functions. It has a critical role as part of nucleic acids (i.e., DNA and RNA) which are essential for cell protein synthesis. Phosphorus is present in phospholipids, the key components in the structure of cell membranes. It is essential in carbohydrate metabolism as the phosphate esters of several compounds. Phosphorylation to glucose 6-phosphate initiates glucose catabolism. Many high-energy phosphate bonds involve phosphoryl groups. Phosphate is part of some conjugated proteins such as casein of milk. Some of the water-soluble vitamins function as coenzymes only when combined with phosphate.
The phosphate buffer system is of importance in the regulation of pH.
Deficiency
A primary deficiency of phosphorus is not known to occur in man. Despite a relatively low intake of phosphorus, a deficiency is rarely seen because it is efficiently recycled by the kidney; about 90% of the filtered phosphate is reabsorbed by the proximal tubule.
Phosphorus metabolism may be disturbed in many types of diseases, notably those involving the kidney and the bone. Hypophosphatemia is associated with the adminis-tration of glucose or total parenteral nutrition (TPN) without sufficient phosphate, excessive use of antacids that bind phosphate, hyperparathyroidism, recovery from diabetic acidosis, alcoholism, and some other conditions. Low serum phosphate level causes muscle weak-ness because the muscle cells are deprived of phosphorus essential for energy metabolism.
Hypophosphatemia may also have profound, deleterious effects on the viability of human red blood cells. It may cause a decrease of red cell 2,3-bisphosphoglycerate (BPG) and ATP. BPG promotes oxygen release from oxygenated hemoglobin. A reduction of concentration of this phosphoric acid ester lowers tissue oxygen by shifting the oxygenated hemoglobin dissociation curve to the left. Tissue hypoxia can result despite a pO2tension in the normal range. Parenteral phosphate is given for critically depleted patients. Because the kidney is capable of excreting 600–900 mg of phosphorus daily, hyperphosphatemia is rare in the absence of chronic renal disease.
Requirement
The Food and Nutrition Board recommends that the daily intake of phosphorus be at least 800 mg/day and approximately equal to the calcium intake. Because phosphorus is widely distributed in foods, there is little possibility of a dietary inadequacy if the food contains sufficient protein and calcium.
C. Magnesium
Magnesium is the fourth most abundant cation in the body and quantitatively it is second to potassium as the intracellular cation. An adult human weighing 70 kg contains 20–28g of magnesium, with about 60–65% of the total present in bone, 27% in muscle, 6–7% in other cells, and approximately 1% in extracellular fluid. The erythrocyte content varies from 4.3 to 6.2 mEq/l (1 mEq/l = 12 mg) depending on the age of the cells. As the red blood cells age, the magnesium content falls slowly. Magnesium ion in erythrocytes and plasma exists in free, complexed, and protein-bound forms. In plasma, the approximate
Inorganic Elements (Minerals) 91
percentages are 55% free, 13% complexed with citrate, phosphate, and other ions, and 32% protein bound. Plasma magnesium concentrations range from 1.4 to 2.4 mg/dl.
Food Sources
Magnesium is widely distributed in foods. Because it is present in chlorophyll, green vegetables are important sources. Whole grains, beans, peas, and some seafoods are rich in magnesium.
Absorption
Absorption occurs largely in the upper part of the small intestine, where about 33% of the ingested magnesium is absorbed. It is excreted primarily by the kidney and is regulated in response to magnesium levels in blood. In healthy adults, the serum magnesium is 1.4 to 1.75 mEq/l, with approximately 20% of the magnesium bound to proteins. When magnesium intake is low, the kidney reabsorbs almost all of the magnesium so that practically none is lost by the body. As a result, variation in dietary intake seldom affects blood levels. Urinary losses increase with the use of diuretics and with the consumption of alcohol.
Functions
Just as calcium is responsible for the integrity of the cell membrane, magnesium is responsible for the structural integrity of the mitochondrial membrane. It is an essential constituent of all soft tissues and bones. The soluble, ionic form participates as a cofactor for countless enzymatic reactions, especially where MgATP is involved. The magnesium-dependent and magnesium-activated enzymes include those of mitochondrial oxidative phosphorylation and of intermediary metabolism of glucose and fatty acids. It plays an important role in neurochemical transmission and muscle excitability. Magnesium plays a vital role in the reversible association of intracellular particles and in the binding of macromolecules to subcellular organelles; for example, the binding of RNA to ribosomes is magnesium dependent.
Deficiency
Because of the wide distribution of magnesium in plant and animal products, primary deficiency of magnesium is rare in individuals with normal organ function. The fall in
Because of the wide distribution of magnesium in plant and animal products, primary deficiency of magnesium is rare in individuals with normal organ function. The fall in