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National Research Council (US) Subcommittee on the Tenth Edition of the Recommended Dietary Allowances. Recommended Dietary Allowances: 10th Edition. Washington (DC): National Academies Press (US); 1989.

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Recommended Dietary Allowances: 10th Edition.

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9Minerals

CALCIUM

The adult body contains approximately 1,200 g of calcium, approximately 99% of which is present in the skeleton. Bone mineral consists of two chemically and physically distinct calcium phosphate pools—an amorphous phase and a loosely crystallized phase. The skeleton contains two major forms of bone: trabecular (spongy) bone, exemplified by the vertebral bodies, and denser cortical bone, such as the femur. Bone is constantly turning over, a continuous process of resorption and formation. In children and adolescents, the rate of formation of bone mineral predominates over the rate of resorption. In later life, resorption predominates over formation. Therefore, in normal aging, there is a gradual loss of bone (Arnaud, 1988).

The remaining 1% of body calcium is found in extracellular fluids, intracellular structures, and cell membranes. This extraskeletal calcium plays an essential role in such vital functions as nerve conduction, muscle contraction, blood clotting, and membrane permeability. Blood calcium concentration is maintained within very narrow limits by the interplay of several hormones (1,25-dihydroxycholecalciferol, parathyroid hormone, calcitonin, estrogen, testosterone, and possibly others), which control calcium absorption and excretion, as well as bone metabolism.

Levels of soft tissue calcium are maintained at the expense of bone in the face of inadequate calcium intake or absorption. Under such circumstances, there is either inadequate mineralization of bone in the young or mineral is withdrawn from bone with a consequent reduction of bone strength.

Calcium is lost from the body in feces, urine, and sweat. The fecal calcium consists of unabsorbed dietary calcium, the amount of which depends on dietary intake and other factors, and a small portion of the endogenously secreted calcium (about 100 to 150 mg/day), which escapes reabsorption. Urinary calcium excretion of adults is about 100 to 250 mg/day, but varies widely among persons consuming self-selected diets (Nordin et al., 1967). Urinary excretion is influenced by hormonal and dietary factors. Among the latter are protein, sodium, and some carbohydrates, which increase calcium excretion, and phosphorus, which decreases it. Except under conditions of extreme sweating, loss of calcium from the skin is small (about 15 mg/day).

Calcium Absorption

Intestinal absorption of calcium is variably influenced by several nutritional and physiological factors (Avioli, 1988). Studies of calcium absorption have frequently been flawed by failure to include the extended period (4 weeks or more) required for adaptation to changes in dietary intake and to control for intervening dietary variables. Nonetheless, the literature is consistent on several points. The efficiency of absorption is increased during periods of high physiologic requirement. Thus, children may absorb up to 75% of ingested calcium as compared to the 20 to 40% typically observed in young adults in the United States. Absorption is impaired in the aged (Heaney et al., 1982). A higher percentage of ingested calcium is absorbed at low intakes than at high intakes. Above an intake of about 800 mg/day in normal adults, absorption is approximately 15% of the amount ingested (Heaney et al., 1975). Vitamin D is a recognized promoter of calcium absorption. The role of protein and phosphorus is less clear. Dietary protein enhances calcium absorption (McCance et al., 1942) in the protein intake range between inadequate and adequate levels, but has little additional effect beyond RDA levels of protein (Chu et al., 1975). The effect of phosphorus differs with the source, but, excluding phytate phosphorus (see below), this element appears to have little if any depressing effect on calcium absorption (Spencer et al., 1978, 1986).

It is uncertain if there are biologically important differences in the absorption of calcium from different foods or diets. In animal models, the presence of lactose tends to enhance paracellular calcium absorption, but this effect has not been consistently demonstrated (Scrimshaw and Murray, 1988). Phytate and oxalate bind calcium, rendering it insoluble, and certain fiber fractions may interfere with calcium absorption. These substances are believed to be of little practical importance at intakes typical for the U.S. diet (Judd et al., 1983; LSRO, 1987; Schwartz et al., 1986).

Dietary Sources and Usual Intakes

Calcium intake varies widely among individuals in the United States but is generally higher in males than in females. The 1977–1978 Nationwide Food Consumption Survey (USDA, 1984) reported an average daily intake of 743 mg for all people, ranging from 530 mg for women 35 to 50 years old to 1,179 mg for 12- to 18-year-old boys. No group of adult females had a calcium intake equal to or greater than the RDA of 800 mg. Black women ingested less dietary calcium than whites (452 compared to 640 mg/day) (USDA, 1987).

Dairy products contribute more than 55% of the calcium intake of the U.S. population (Block et al., 1985). Other contributors to the daily intake of calcium are some leafy green vegetables (such as broccoli, kale, and collards), lime-processed tortillas, calcium-precipitated tofu, and calcium-fortified foods. Bones, especially the soft bones of fish (e.g., sardines, salmon) and tips of poultry leg bones, are rich and often unrecognized sources of calcium. Water is a variable source. Several proprietary antacid preparations are calcium salts that may constitute an underreported calcium source.

Bone Formation and Retention

Although calcium is a major constituent of bone, it is only one of many factors affecting bone health. Genetic influences determine bone mass; sex hormones and physical activity influence bone metabolism. Many dietary constituents are either essential for, or complementary to, the proper utilization of calcium, including vitamin D (Parfitt et al., 1982), copper (Davis and Mertz, 1987), zinc (Hambidge et al., 1986), manganese (Hurley and Keen, 1987), fluorine (Krishnamachari, 1987), silicon (Carlisle, 1986), and boron (Nielsen, 1987).

The growth of the skeleton requires a positive calcium balance until peak bone mass is reached. Mineralization of bone continues for some years after longitudinal bone growth has ceased. Most of the accumulation of bone mineral occurs in humans by about 20 years of age, but some bone mineral is added during the third decade. Bone mass then begins to decline slowly during the fifth decade in both sexes, as evidenced by progressive reduction of bone density. The rate of loss accelerates greatly about the time of menopause in women and remains high for several years. Bone loss accelerates much later in men (by a decade or more). This results in gradually diminishing bone strength and increased risk of fractures. The risk of fracture is less at a given age in people who have achieved larger bone mass during the period of bone mass accretion than in those with lower peak bone mass (Arnaud, 1988; Heaney, 1986).

Peak bone mass appears to be related to intake of calcium during the years of bone mineralization. Investigations have usually involved estimation of past calcium intake from a history of food consumption patterns, in which differing habitual milk consumption is the chief contributor to differences in calcium intake. Thus, intakes of other nutrients (e.g., protein, phosphorus, and, importantly, the vitamin D added to most milk in the United States) are likely to covary with calcium. In a study of two population groups in Yugoslavia with different, long-standing intake patterns (500 and 1,100 mg of calcium per day), greater bone mass was found at all ages and in both sexes in the high calcium community (Matkovic et al., 1979). Since the rate of bone loss was the same in adults of the two communities, the finding of more bone mass in the older age groups of the high-calcium district must reflect higher peak bone mass attainment. In studies conducted in the United States, investigators have reported significant correlations between current bone density and past milk or calcium intake in adult women (Halious and Anderson, 1989; Hurxthal and Vose, 1969; Sandler et al., 1985). In another U.S. study, present calcium intake was compared with bone density of postmenopausal women in two Iowa communities where the water supply contained different levels of calcium over at least a 50–year period (60 compared to 375 mg/liter), resulting in average calcium intakes of 964 compared to 1,326 mg/day, respectively (Sowers et al., 1985). There were no detectable differences in measured bone density between communities. After adjustment for confounding factors, there was a small but significantly higher bone density in the Iowa women who currently consumed both 800 mg or more of calcium and 400 IU or more of vitamin D per day. There is, however, no clear evidence that bone density of postmenopausal women is related to concurrent dietary calcium intake within a wide range (Garn, 1970; Garn et al., 1969) except, perhaps, where this reflects a high-calcium food consumption pattern established in childhood.

The postmenopausal rate of decline in bone mineral is strongly dependent on estrogen status. Estrogen replacement slows the rate of bone loss. Evidence that supplementary calcium (1.5 to 2.5 g/day) can retard the rate of postmenopausal bone loss is mixed (NRC, 1989), but the balance of evidence suggests that calcium alone has only a small effect on cortical bone loss and none on trabecular bone (Freudenheim, 1986; Riis et al., 1987). Combined daily treatment with 0.3 mg of conjugated estrogens plus 1 g of calcium supplement has, however, been reported to be as effective as 0.6 mg of conjugated estrogen (widely accepted to be the minimum effective dose for prevention of bone loss) without added calcium (Ettinger et al., 1987). The observed inverse relationship between body weight and risk of hip fracture in older women (heavier women having less risk of fracture) may be due in part to the maintenance of higher levels of estrogen by peripheral conversion of precursor steroids to estrogen in adipose tissue (Kiel et al., 1987).

In the subcommittee's judgment, the most promising nutritional approach to reduce the risk of osteoporosis in later life is to ensure a calcium intake that allows the development of each individual's genetically programmed peak bone mass during the formative years. The importance of meeting recommended allowances at all ages is stressed, but with special attention to intakes throughout childhood to age 25 years.

Relationship to Phosphorus and Protein Intakes

The level of dietary protein and phosphorus can affect the metabolism of, and requirement for, calcium, primarily as a result of their opposing effects on urinary calcium brought about by changes in fractional tubular reabsorption of calcium. The effect on urinary excretion outweighs the small effects on absorption described above. An increase in protein intake reduces fractional tubular reabsorption (Allen et al., 1979; Kim and Linkswiler, 1979) and results in an increase in urinary calcium excretion (Johnson et al., 1970; Margen et al., 1974). In contrast, an increase in phosphorus intake increases fractional reabsorption and causes urinary calcium to decrease (Hegsted et al., 1981; Spencer et al., 1978). Because of the opposing effects of protein and phosphorus on urinary calcium and calcium retention, a simultaneous increase in the intake of both, a pattern characterized by milk, eggs, and meat ingestion, has but little effect on calcium balance at recommended levels of calcium intake (Spencer et al., 1988).

The low ratio of calcium to phosphorus in the U.S. diet was of concern in the past. Animal studies indicated that excessive phosphorus intake led to secondary hyperparathyroidism, resulting in loss of calcium from the skeleton (LSRO, 1981). This effect was not seen in monkeys (Anderson et al., 1977), and studies in humans have failed to demonstrate effects of dietary phosphorus intake on calcium balance at adequate levels of calcium intake (Spencer et al., 1988).

Other Potential Functions

A high intake of calcium has been associated with lower blood pressure in some studies (McCarron et al., 1984), but not in others (Ackley et al., 1983). Animal studies show that high levels of dietary calcium protect against cell proliferation in the colon induced by fat and bile acids (Bird, 1986; Wargovich et al., 1983). The evidence from human studies is, however, insufficient to support an inference that high calcium diets protect against the development of colon tumors. These subjects are reviewed in the Food and Nutrition Board report Diet and Health (NRC, 1989).

Recommended Allowances

Adults and Adolescents An optimal calcium intake is difficult to define, given the substantial adaptive capacity and the long lag period before changes in status can be detected. It is not surprising that recommendations in different countries vary widely, from a low of 400 mg/day for women in Thailand to a high of 1,000 mg for both sexes over 75 years of age in the Netherlands. Concern for the high proportion of postmenopausal women at risk for osteoporosis has led some to suggest that the RDA for calcium should be increased markedly (NIH, 1984). This subcommittee is not persuaded by the evidence in hand that the long-standing RDAs should be revised upward in response to this medical concern. Nor is the subcommittee convinced that levels should be lowered to those recommended by international groups (e.g., FAO, 1962) despite the evidence that many population groups seemingly maintain satisfactory status with much lower intakes of calcium than the RDA.

The age at which peak bone mass is attained is uncertain, but probably is not less than 25 years. The subcommittee thus recommends an extra calcium allowance to permit full mineral deposition through age 24 rather than through age 18 years, as in previous editions of the RDA.

The recommended calcium allowance for adults is based on an estimate of 200 to 250 mg/day of obligatory loss and an estimated absorption rate of 30 to 40%. Calcium accretion during the growing years averages 140 to 165 mg/day and may be as high as 400 to 500 mg/day during the pubertal growth period (Garn, 1970). Intestinal calcium absorption is efficient in youth and adapts in relation to needs. In setting the RDA, however, the absorption rate is conservatively estimated to be 40%.

An intake of 1,200 mg is recommended for both sex groups from ages 11 to 24 years. For older age groups, the previous allowance of 800 mg is retained. These amounts of calcium can easily be obtained if dairy products are included in the diet. A balanced diet furnishes, in addition to calcium, other nutrients necessary for bone health. The subcommittee emphasizes that its recommendations do not address the possible needs of persons who may have osteoporosis and should receive medical attention.

Pregnancy and Lactation The newborn contains approximately 30 g of calcium, most of which is deposited during the third trimester of intrauterine development (Pitkin, 1985). Calcium retention is 200 to 250 mg/day during that period. Human milk contains approximately 320 mg calcium/liter. This concentration corresponds to 240 mg in the average daily milk secretion of 750 ml; 300 mg encompasses the probable upper boundary of production (+ 2 SDs).

The calcium absorption rate has been reported to increase during pregnancy and lactation in rats (Halloran and DeLuca, 1980) and adolescent girls (Heaney and Skillman, 1971). There is no clear relation between women's bone health and either their number of pregnancies or lactation history in populations that consume currently recommended amounts of calcium (Koetting and Wardlaw, 1988; Lambke et al., 1977). This evidence suggests it is prudent to recommend a calcium intake of 1,200 mg throughout pregnancy and lactation, irrespective of age.

Infants and Children Infants thrive on an average intake of 240 mg of calcium from 750 ml of human milk, of which they retain approximately two-thirds. Allowing 25% for variance, intake would be 300 mg, of which 200 mg is absorbed. The retention of calcium from formulas based on cow's milk is less than one-half. Therefore, the recommendation for formula-fed infants is 400 mg/day for the first 6 months of life. This amount is provided by typical infant formulas now in use in the United States. An allowance of 600 mg/day would suffice for the next 6 months and 800 mg/day at ages 1 to 10 years. These latter allowances are arbitrary, since specific data on requirements of this age group are lacking.

Excessive Intakes and Toxicity

Although no adverse effects have been observed in many healthy adults consuming up to 2,500 mg of calcium per day, high intakes may induce constipation and place up to half of otherwise healthy hypercalciuric males at increased risk of urinary stone formation. A high calcium intake may inhibit the intestinal absorption of iron, zinc, and other essential minerals (Greger, 1988). Ingestion of very large amounts may result in hypercalciuria, hypercalcemia, and deterioration in renal function in both sexes (Avioli, 1988). Supplementation to a total calcium intake much above the RDA is not recommended.

References

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PHOSPHORUS

Phosphorus is an essential component of bone mineral, where it occurs in the mass ratio of 1 phosphorus to 2 calcium. Approximately 85% (700 g) of the phosphorus in the adult body is found in bone. Phosphorus also plays an important role in many and varied chemical reactions in the body. It is present in soft tissues as soluble phosphate ion; in lipids, proteins, carbohydrates, and nucleic acid in an ester or anhydride linkage; and in enzymes as a modulator of their activities. Energy for metabolic processes derives largely from the phosphate bonds of adenosine triphosphate (ATP), creatine phosphate, and similar compounds.

Phosphorus is efficiently absorbed by the small intestine as free phosphate (Avioli, 1988). Phosphorus absorption probably takes place by three different mechanisms: (1) calcium-coupled, vitamin D-dependent; (2) noncalcium-coupled, vitamin D-dependent; and (3) noncalcium coupled, vitamin D-independent (Parfitt and Kleerekoper, 1980).

Infants absorb from 65 to 70% of the phosphorus in cow's milk and 85 to 90% of that in human milk. Children and adults absorb 50 to 70% of the phosphorus in normal diets and as much as 90% when the intake is low (LSRO, 1981).

Polyphosphate (sodium hexametaphosphate), which is used in the processing of food, is efficiently hydrolyzed to orthophosphate in the intestine, where it is well absorbed (Zemel and Linkswiler, 1981). Approximately 50% of phytate phosphorus is absorbed (Parfitt et al., 1964).

Dietary Sources and Usual Intakes

Phosphorus is present in nearly all foods. The amount available in the food supply from unprocessed primary commodities, about 1,430 to 1,520 mg per capita per day, has been relatively constant during the past 75 years, despite marked changes in food consumption patterns (Bunch, 1987). The mean daily phosphorus intake is approximately 1,500 mg/day for adult males (USDA, 1986) and 1,000 mg/day for adult females (USDA, 1987). True intakes may be 15 to 20% higher, however, since the phosphorus supplied by numerous food additives in processed foods is typically not accounted for in tables of food composition (Oenning et al., 1988).

Major contributors of phosphorus are protein-rich foods and cereal grains. About half the food phosphorus in the U.S. diet comes from milk, meat, poultry, and fish. Cereal products contribute about 12%. Diets based heavily on convenience foods may derive 20 to 30% of phosphorus from food additives (Greger and Krystofiak, 1982).

Meats, poultry, and fish, exclusive of bone, contain 15 to 20 times more phosphorus than calcium. There is twice as much phosphorus as calcium in eggs, grains, nuts, dry beans, peas, and lentils. Only milk, natural cheeses, green leafy vegetables, and bone contain more calcium than phosphorus. Cow's milk contains both more calcium and phophorus than does human milk, and the ratios of the elements differ widely. The ratio of calcium to phosphorus in cow's milk is 1.3 to 1 and that in human milk is 2.3 to 1.

The calcium-to-phosphorus ratio in the U.S. diet varies, depending on food consumption patterns. The calcium-to-phosphorus ratio is higher in diets of infants and children than in diets of adults. The average ratio is 1 to 1.8 for adults between 35 to 50 years of age (USDA, 1984), but may be as low as 1 to 4 for those whose diets are low in dairy products and green vegetables.

General Signs of Deficiency

Because almost all foods contain phosphorus, dietary phosphorus deficiency does not usually occur. An exception is small premature infants fed human milk exclusively. Such infants need more phosphorus than is contained in human milk for the rate of bone mineralization required (Von Sydow, 1946). Without additional phosphorus, hypophosphatemic rickets may develop (Rowe et al., 1979).

Serious phosphorus deficiency has been induced in patients receiving aluminum hydroxide as an antacid for prolonged periods (Bloom and Flinchum, 1960; Lotz et al., 1968). Aluminum hydroxide binds phosphorus, making it unavailable for absorption. Phosphorus deficiency results in bone loss and is characterized by weakness, anorexia, malaise, and pain.

Recommended Allowances

Adults, Children, and Pregnant and Lactating Women The precise requirement for phosphorus is unknown. Previous editions have set the allowance for phosphorus equal to calcium for all ages except the young infant. Although dietary phosphorus is more abundant than calcium in most U.S. diets with the few exceptions cited, neither inadequate nor excessive intake of phosphorus appears to be a problem. The subcommittee accepts that a 1-to-1 ratio of calcium to phosphorus will provide sufficient phosphorus for most age groups, but if the calcium intake is adequate, the precise ratio of these minerals is unimportant. The RDA for phosphorus is 800 mg for children 1 to 10 years, 1,200 mg for ages 11 to 24 years, and 800 mg for ages beyond 24. A total allowance of 1,200 mg/day is recommended during pregnancy and lactation.

Infants The phosphorus content of human milk, 14 mg/100 g, is adequate for the full-term infant; the calcium-to-phosphorus ratio is 2.3 to 1. The RDA for calcium in infants is based on the poorer absorption of calcium from formulas than from human milk. Allowances for phosphorus are based on a calcium-to-phosphorus ratio of 1.3 to 1 (the same as in cow's milk) during the first 6 months, and 1.2 to 1 for the second 6 months. This declining ratio is consistent with the gradual addition of supplementary foods to the basic milk diet of the newborn. The RDA of formula-fed infants from birth to 6 months of age is 300 mg/day, and that for infants 6 to 12 months is 500 mg/day.

Excessive Intakes and Toxicity

An excess of phosphorus, i.e., a calcium-to-phosphorus ratio lower than 1 to 2, has been shown in several species of animals to lower the blood calcium level and to cause secondary hyperparathyroidism with resorption and loss of bone. In humans, only the effect on blood calcium level has been observed clinically. High-phosphorus human milk substitutes may contribute to the occurrence of hypocalcemic tetany in early infancy (Mizraki et al., 1968), unless calcium levels are increased commensurately. The phosphorus levels present in normal diets are not likely to be harmful—certainly not in the presence of adequate intakes of calcium and vitamin D.

References

  • Avioli, L.V. 1988. Calcium and phosphorus. Pp. 142–158 in M.E. Shils, editor; and V.R. Young, editor. , eds. Modern Nutrition in Health and Disease, 7th ed. Lea & Febiger, Philadelphia.
  • Bloom, W.L., and D. Flinchum. 1960. Osteomalacia with pseudofractures caused by the ingestion of aluminum hydroxide. J. Am. Med. Assoc. 174: 1327–1330.
  • Bunch, K.L. 1987. Food consumption, prices, and expenditures. 1987. Statistical Bulletin No. 749. U.S. Department of Agriculture, Washington, D.C.
  • Greger, J.L., and M. Krystofiak. 1982. Phosphorus intake of Americans. Food Technol. 36: 78–84.
  • Lotz, M., E. Zisman, and F.C. Bartter. 1968. Evidence for a phosphorus-depletion syndrome in man. N. Engl. J. Med. 278: 409–415. [PubMed: 5636663]
  • LSRO (Life Sciences Research Office). . Effects of Dietary Factors on Skeletal Integrity in Adults: Calcium, Phosphorus, Vitamin D and Protein. Federation of American Societies for Experimental Biology, Bethesda, Md. [PubMed: 6862034]
  • Mizraki, A., R.D. London, and D. Gribetz. 1968. Neonatal hypocalcemia: its causes and treatment. N. Engl. J. Med. 278: 1163–1165. [PubMed: 5689577]
  • Oenning, L.L., J. Vogel, and M.S. Calvo. 1988. Accuracy of methods estimating calcium and phosphorus intake in daily diets. J. Am. Diet. Assoc. 88: 1076–1078. [PubMed: 3418003]
  • Parfitt, A.M., and M. Kleerekoper. 1980. The divalent ion homeostatic system—physiology and metabolism of calcium, phosphorus, magnesium, and bone. Pp. 269–398 in M.H. Maxwell, editor; and C.R. Kleeman, editor. , eds. Clinical Disorders of Fluid and Electrolyte Metabolism, 3rd ed. McGraw-Hill, New York.
  • Parfitt, A.M., B.A. Higgins, J.R. Nassim, J.A. Collins, and A. Hilb. 1964. Metabolic studies in patients with hypercalciuria. Clin. Sci. 27: 463–482. [PubMed: 14236784]
  • Rowe, J.C., D.H. Wood, D.W. Rowe, and L.G. Raisz. 1979. Nutritional hypophosphatemic rickets in a premature fed breast milk. N. Engl. J. Med. 299: 293–296. [PubMed: 759883]
  • USDA (U.S. Department of Agriculture). 1984. Table 2A-1: Nutritive value of food intake. Average per individual per day, 1/1977–78. Pp. 154–155 in Nationwide Food Consumption Survey. Nutrient Intakes: Individuals in 48 States, Year 1977–78. Report No. I-2. Consumer Nutrition Division, Human Nutrition Information Service. U.S. Department of Agriculture, Hyattsville, Md.
  • USDA (U.S. Department of Agriculture). 1986. Nationwide Food Consumption Survey. Continuing Survey of Food Intakes by Individuals. Men 19–50 Years, 1 Day, 1985. Report No. 85-3. Nutrition Monitoring Division, Human Nutrition Information Service. U.S. Department of Agriculture, Hyattsville, Md. 94 pp.
  • USDA (U.S. Department of Agriculture). 1987. Nationwide Food Consumption Survey. Continuing Survey of Food Intakes by Individuals. Women 19–50 Years and Their Children 1–5 Years, 4 Days, 1985. Report No. 85-4. Nutrition Monitoring Division, Human Nutrition Information Service. U.S. Department of Agriculture, Hyattsville, Md. 182 pp.
  • Von Sydow, G. 1946. A study of the developments of rickets in premature infants. Acta Paediatr. Scand. 33 Suppl. 2: 3.
  • Zemel, M.B., and H.M. Linkswiler. 1981. Calcium metabolism in the young adult male as affected by level and form of phosphorus intake and level of phosphorus intake. J. Nutr. 111: 315–324. [PubMed: 6257868]

MAGNESIUM

Approximately 40% of the 20 to 28 g of magnesium contained in the adult human body resides in the muscles and soft tissues, about 1% in the extracellular fluid, and the remainder in the skeleton (Aikawa, 1981). Average plasma magnesium concentration is about 0.85 mM (range, 0.65 to 1.0 mM) (Lowenstein and Stanton, 1986). This level is maintained remarkably constant in healthy individuals by poorly understood homeostatic mechanisms.

Numerous biochemical and physiological processes require or are modulated by magnesium. As the complex Mg-ATP2−, magnesium is essential for all biosynthetic processes, glycolysis, formation of cyclic-AMP, energy-dependent membrane transport, and transmission of the genetic code (Eichhorn and Marzilli, 1981; Rude and Oldham, 1987; Wacker, 1980; Wester, 1987). More than 300 enzymes are known to be activated by magnesium, either by interaction between substrate and an active site or by induction of conformational change (Garfinkel and Garfinkel, 1985; Mildvan, 1970; Wacker, 1980). Free intracellular magnesium concentrations have been estimated at 0.3 to 1.0 mM (Cittadini and Scarpa, 1983) and are believed to control cellular metabolism by modulating the activity of rate-limiting enzymes (Garfinkel and Garfinkel, 1985; Wacker, 1980). Extracellular magnesium concentrations are critical to the maintenance of electrical potentials of nerve and muscle membranes and for transmission of impulses across neuromuscular junctions (Aikawa, 1981). In these processes, which also depend on calcium, the two cations may act synergistically or antagonistically (Iseri and French, 1984; Livingston and Wacker, 1976).

Magnesium homeostasis does not appear to be regulated by hormonal mechanisms. Plasma magnesium levels are believed to be regulated primarily by the kidney (Heaton, 1969; Quamme, 1986). Approximately 70% of plasma magnesium is not bound to protein and is therefore filterable (Walser, 1967). About 30% of filtered magnesium is reabsorbed in the proximal tubule and another 65% is reabsorbed in the loop of Henle, the site at which major adjustments in response to plasma concentrations appear to take place. A portion of bone magnesium is in passive equilibrium with that in the plasma (Alfrey et al., 1974) and acts as a buffer against fluctuations in extracellular magnesium concentrations.

The rare occurrence of a genetic defect in magnesium absorption in infants (Paunier et al., 1965) suggests that a specific mechanism exists for magnesium absorption (Roth and Werner, 1979), but none has yet been identified. Magnesium secreted into the gut is efficiently reabsorbed. Only 25 to 50 mg of endogenous magnesium are normally excreted in the feces. Fractional magnesium absorption changes inversely with magnesium intake (Graham et al., 1960; Roth and Werner, 1979). Average net magnesium absorption is about 50% (range, 40 to 60%) of intake (Schwartz et al., 1978, 1984; Wilkinson, 1976). The presence of phytate or fiber may reduce magnesium absorption to a minor degree (Kelsay et al., 1979; Reinhold et al., 1976; Schwartz et al., 1984).

General Signs of Deficiency

Magnesium depletion with or without symptoms has been reported in association with numerous disease states (Shils, 1988). Most of these fall into one of four categories: gastrointestinal tract abnormalities associated with malabsorption or excessive fluid and electrolyte losses; renal dysfunction with defects in cation reabsorption; general malnutrition and alcoholism; and iatrogenic causes such as nasogastric suctioning, intravenous or intragastric feeding of mixtures deficient in magnesium, or use of drugs that interfere with magnesium conservation.

Purely dietary magnesium deficiency has not been reported in people consuming natural diets and has been induced experimentally only once (Shils, 1988). In that study, seven patients were fed a formula diet after radical surgery for oral cancer (Shils, 1969). After a month on a formula that supplied adequate magnesium, the formula was changed to supply 12 mg of magnesium. Urinary magnesium fell sharply to levels no longer detectable within a week, demonstrating the efficiency of renal conservation. Fecal magnesium losses were also very low. Nonetheless, plasma magnesium fell continuously. Symptoms were noted at different times after depletion began, the earliest onset occurring in two people after 24 and 26 days. Others remained asymptomatic for more than 100 days, but all eventually showed symptoms. The most prominent and consistent signs were nausea, muscle weakness, irritability, mental derangement, and myographic changes, but not all symptoms were observed in all patients. The signs described by Shils do not coincide entirely with those reported in patients who spontaneously develop symptomatic hypomagnesemia, which is frequently complicated by other deficiencies or diseases (Wacker, 1980). Both hypokalemia and hypocalcemia developed in Shils's patients, although the diet was adequate in potassium and calcium, which led him to conclude that magnesium is important to calcium and potassium homeostasis—a concept still valid today.

Dietary Sources and Usual Intakes

All unprocessed foods contain magnesium, albeit in widely differing amounts. The highest concentrations of magnesium are found in whole seeds such as nuts, legumes, and unmilled grains (Seelig, 1964). More than 80% of the magnesium is lost by removal of the germ and outer layers of cereal grains (Marier, 1986). Green vegetables are another good source of magnesium, much of it in the form of the magnesium-porphyrin complex chlorophyll. Fish, meat, and milk are relatively poor sources of magnesium. So are most commonly eaten fruits, with the exception of bananas. On the whole, diets high in vegetables and unrefined grains are much higher in magnesium than diets that include substantial quantities of refined foods, meat, and dairy products (Abdullah et al., 1981; Marier, 1986).

Average intakes of magnesium have tended to decline in the United States. Per capita magnesium in the U.S. food supply (estimated as food flowing through the food distribution system) was 408 mg/day during the period 1909 to 1913 (Welsh and Marsten, 1982). By 1949, the amount had declined to 368 mg. The amount reported in 1980 was 349 mg of magnesium. These estimates are in close agreement with data reported by Pennington et al. (1984). Chemical analyses of typical diets in the Food and Drug Administration's Total Diet Study showed that the reference adult male, assumed to need 2,850 kcal/day, would have received 354, 328, 326, and 343 mg of magnesium during 1976, 1977, 1980, and 1981–1982, respectively. In 1985, the average magnesium intake of adult men was 329 mg (USDA, 1986), whereas mean intakes for adult women and children 1 to 5 years of age were 207 and 193 mg, respectively (USDA, 1987).

Recommended Allowances

The only practical method for estimating human magnesium requirements is the metabolic balance procedure. Neither the short-lived radioisotope 28Mg nor the stable isotope 26Mg is suitable for whole-body magnesium turnover studies (Schwartz et al., 1978). The other possible alternative for the estimation of requirements (assessment of intake in relation to magnesium status) is unsatisfactory, because there are no reliable noninvasive techniques for determining magnesium status (Elin, 1987; Ryzen et al., 1985).

Adults Balance data reviewed by Seelig (1964) led her to conclude that an intake of 6.0mg/kg per day is needed to ensure adequate magnesium status. Many of the studies she reviewed were conducted before the common use of atomic absorption spectrometry for magnesium analyses. Later studies indicate that magnesium balance can be maintained in healthy men at intakes as low as 3.0 to 4.5 mg/kg (210 to 320 mg/day) (Greger and Baier, 1983; Hunt and Schofield, 1969; Mahalco et al., 1983; Schwartz et al., 1984, 1986).

The subcommittee considered both balance data and the usual intakes of the U.S. population in setting RDAs. Although dietary surveys indicate that magnesium intakes of some segments of the population are lower than current recommendations, there is no unequivocal evidence that magnesium deficiency is a problem among healthy persons in this country. The RDA for adults of both sexes is accepted to be 4.5 mg/kg, the upper range of requirements determined in modern balance studies. This value is approximately the same as the 1980 RDA—280 mg for women and 350 mg for men ages 19 and above.

Pregnancy and Lactation Hathaway (1962) concluded from a compilation of previous data that an intake of 350 mg/day is sufficient to meet the needs of mother and fetus. In a later study, 10 pregnant women on self-selected diets supplying 269 ± 55 mg/day were found, on average, to be in negative magnesium balance (Ashe et al., 1979). Underestimation of intake may have been a contributing factor to negative magnesium (and calcium) balances in this study, since magnesium content of water was not measured.

A healthy full-term fetus is reported to contain approximately 1 g of magnesium (Widdowson and Dickerson, 1964; Ziegler et al., 1976). Most of this is acquired in the last two trimesters of pregnancy at an estimated average rate of about 6 mg/day. An increase of 20 mg of magnesium in the daily recommendation for pregnancy should be enough to meet the needs of the fetus and maternal tissue growth, allowing for individual variation and assuming 50% of dietary magnesium to be absorbed.

Human milk contains about 28 to 40 mg magnesium per liter (Lemons et al., 1982), or about 30 mg in the average volume of 750 ml per day. In the first 6 months of lactation, 60 mg of dietary magnesium per day would replenish average magnesium lost in milk, assuming 50% absorption. To allow for variation, the RDA is 25% higher (+ 2 SDs), or 75 mg/day in addition to the nonlactating allowance. By the same reasoning, the increase in the RDA for the second 6 months of lactation is 60 mg. These allowances for pregnancy and lactation are far lower than in previous editions. The derivation of previous recommendations was not specified.

Infants and Children There are no data on magnesium requirements of young children. In the first 6 months of life, average magnesium intake of breastfed infants is 30 mg/day. To allow for variability in growth, (2 SDs = 25%), the allowance is 40 mg/day. The allowance for the second 6 months is increased to 60 mg/day. Schwartz et al. (1973) reported that a minimum magnesium intake of 4.6 mg/kg per day was sufficient to support balance in boys aged 13 to 16 years. Greger et al. (1978) found small negative balances in adolescent girls on magnesium intakes of 3.3 to 5.6 mg/kg. The allowance recommended for children of both sexes between 1 and 15 years is 6.0 mg/kg per day, which is substantially lower than the 1980 RDAs for these groups. Allowances for the 15- to 18-year group are maintained at 400 and 300 mg for males and females, respectively, as in the previous edition.

Excessive Intakes and Toxicity

There is no evidence that large oral intakes of magnesium are harmful to people with normal renal function, but impaired renal function resulting in magnesium retention is often associated with hypermagnesemia. Early symptoms of hypermagnesemia include nausea, vomiting, and hypotension. As the condition worsens, bradycardia, cutaneous vasodilatation, electrocardiographic changes, hyporeflexia, and central nervous system depression ensue. At the most severe level of hypermagnesemia, respiratory depression, coma, and asystolic arrest may occur (Mordes and Wacker, 1978).

Most cases of hypermagnesemia occur following the therapeutic use of magnesium-containing drugs. Antacids and laxatives containing relatively low amounts of magnesium generally are regarded as safe.

References

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Copyright © 1989 by the National Academy of Sciences.
Bookshelf ID: NBK234927

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