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TABLE 1 Dietary Reference Intakes for Magnesium by Life Stage Group DRI values (mg/day) EARa RDAb AIc ULd,e males females males females males females Life stage group NDf 0 through 6 mo 30 30 7 through 12 mo 75 75 ND 1 through 3 y 65 65 80 80 65 4 through 8 y 110 110 130 130 110 9 through 13 y 200 200 240 240 350 14 through 18 y 340 300 410 360 350 19 through 30 y 330 255 400 310 350 31 through 50 y 350 265 420 320 350 51 through 70 y 350 265 420 320 350 > 70 y 350 265 420 320 350 Pregnancy £ 18 y 335 400 350 19 through 30 y 290 350 350 31 through 50 y 300 360 350 Lactation £ 18 y 300 360 350 19 through 30 y 255 310 350 31 through 50 y 265 320 350 a EAR = Estimated Average Requirement. b RDA = Recommended Dietary Allowance. c AI = Adequate Intake. d UL = Tolerable Upper Intake Level. Unless otherwise specified, the UL represents total intake from food, water, and supplements. e The ULs for magnesium represent intake from pharmacological agents only and do not include intake from food and water. f ND = Not determinable. This value is not determinable due to the lack of data of adverse effects in this age group and concern regarding the lack of ability to handle excess amounts. Source of intake should only be from food to prevent high levels of intake.

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PART III: MAGNESIUM 341 MAGNESIUM M agnesium is involved in more than 300 enzymatic processes in the body, as well as in bone health and in the maintenance of intracellu- lar levels of potassium and calcium. Magnesium also plays a role in the development and maintenance of bone and other calcified tissues. Magnesium requirements for adults are based primarily on balance stud- ies. The Tolerable Upper Intake Level (UL) is based on diarrhea as the critical endpoint and was derived from several studies on adults evaluating the effect of high magnesium intake from nonfood sources. DRI values are listed by life stage group in Table 1. Foods rich in magnesium include green leafy vegetables, whole grains, and nuts. Magnesium may be poorly absorbed from foods that are high in fiber and phytic acid. Magnesium deficiency may result in muscle cramps, hypertension, and coronary and cerebral vasospasms. Adverse effects from excess intake of magnesium from food sources are rare, but the use of pharmacological doses of magnesium from nonfood sources can result in magnesium toxicity, which is characterized by diarrhea, metabolic alkalosis, hypokalemia, paralytic ileus, and cardiorespiratory arrest. MAGNESIUM AND THE BODY Function Magnesium is involved in more than 300 enzymatic processes in the body, as well as in the maintenance of intracellular levels of potassium and calcium. Magnesium also plays a role in the development and maintenance of bone and other calcified tissues. Absorption, Metabolism, Storage, and Excretion Magnesium is absorbed along the entire intestinal tract, with maximal absorp- tion likely occurring at the distal jejunum and ileum. In both children and adults, fractional magnesium absorption is inversely proportional to the amount of magnesium consumed. That is, the more magnesium consumed, the lower the proportion that is absorbed (and vice versa). This may be explained by how magnesium is absorbed in the intestine, which is via an unsaturable passive and saturable active transport system.

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DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS 342 To a small extent, vitamin D appears to enhance intestinal magnesium ab- sorption. The body’s level of magnesium is maintained primarily by the kid- neys, where magnesium is filtered and reabsorbed. Approximately 50–60 per- cent of total body magnesium is stored in bone. Magnesium intake in excess of need is efficiently excreted in urine. DETERMINING DRIS Determining Requirements The adult requirements for magnesium are based on dietary balance studies of magnesium. Although several magnesium balance studies have been performed, not all have met the requirements of a well-designed investigation. The mini- mum requirements for the balance studies used to determine the EAR included either an adaptation period of at least 12 days or a determination of balance made while subjects consume self-selected diets. The disadvantage of the latter is that they do not provide the two levels of intakes needed to determine the dose–response relationship. Criteria for Determining Magnesium Requirements, by Life Stage Group Life stage group Criterion 0 through 6 mo Human milk content 7 through 12 mo Human milk + solid food 1 through 8 y Extrapolation of balance studies in older children 9 through 70 y Balance studies > 70 y Intracellular studies; decreases in absorption; balance studies in other adult ages Pregnancy £ 18 y through 50 y Age-specific requirement + gain in lean mass Lactation £ 18 y through 50 y Balance studies The UL The Tolerable Upper Intake Level (UL) is the highest level of magnesium taken acutely without food that is likely to pose no risk of adverse effects for almost all people. Members of the general population should not routinely exceed the UL. When ingested as a naturally occurring substance in foods, magnesium has not been shown to exert any adverse effects. However, adverse effects of

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PART III: MAGNESIUM 343 excessive magnesium intake have been observed with intakes from nonfood sources, such as various magnesium salts used for pharmacological purposes. Therefore, the UL for magnesium represents acute intake from pharmacological agents and does not include intake from food and water. The UL for adults is based on diarrhea as the critical endpoint and was derived from several studies on adults that evaluated the effects of excessive magnesium intake from non- food sources. Although a few studies have noted mild diarrhea and other mild gastrointes- tinal complaints in a small percentage of patients at levels of 360–380 mg/day, it is noteworthy that many other individuals have not encountered such effects, even when receiving substantially more than this amount of supplementary magnesium. Using data from the 1986 National Health Interview Survey (NHIS), it is estimated that almost 1 percent of all adults in the United States took a nonfood magnesium supplement that exceeded the UL of 350 mg/day. The data on supple- ment use also indicated that at least 5 percent of young children who used magnesium supplements exceeded the UL for magnesium at 5 mg/kg/day. How- ever, based on the reported frequency of intake in children, fewer than 1 per- cent of all children would be at risk for adverse effects. More information on supplement use by specific ages is needed. Special Considerations Individuals with certain conditions: People with neonatal tetany, hyperurice- mia, hyperlipidemia, lithium toxicity, hyperthyroidism, pancreatitis, hepatitis, phlebitis, coronary artery disease, arrhythmia, and digitalis intoxication may benefit from the clinically prescribed use of magnesium in quantities exceeding the UL. DIETARY SOURCES Foods Foods rich in magnesium include green leafy vegetables, whole grains, and nuts. Meats, starches, and milk are intermediate in magnesium content, and refined foods generally have the lowest magnesium content. According to the 1989 Total Diet Study of the U.S. Food and Drug Administration, approxi- mately 45 percent of dietary magnesium was obtained from vegetables, fruits, grains, and nuts, whereas approximately 29 percent was obtained from milk, meat, and eggs. With the increased consumption of refined and processed foods, dietary magnesium intake appears to have decreased over the years. Total magnesium

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DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS 344 intake usually depends on calorie intake, which explains the higher intake lev- els generally seen in young children and adult males and the lower intake levels seen in women and the elderly. Water is a variable source of magnesium intake. Typically, “hard” water has a higher concentration of magnesium salts than “soft” water. Dietary Supplements According to the 1986 NHIS, about 14 percent of men and 17 percent of women took supplements that contained magnesium, while approximately 8 percent of young children (2 to 6 years of age) did so. Women and men who used magnesium supplements took similar doses, about 100 mg/day, although the 95th percentile of intake was somewhat higher for women (400 mg/day) than it was for men (350 mg/day). Children who took magnesium had a median daily intake of 23 mg and a 95th-percentile daily supplemental intake of 117 mg. Bioavailability In a typical diet, approximately 50 percent of the magnesium consumed will be absorbed. High levels of dietary fiber from fruits, vegetables, and grains de- crease magnesium absorption or retention, or both. Dietary Interactions There is evidence that magnesium may interact with certain other nutrients and dietary substances (see Table 2). TABLE 2 Potential Interactions with Other Dietary Substances Substance Potential Interaction Notes SUBSTANCES THAT AFFECT MAGNESIUM Phytic acid Phytic acid, or phytate, may Foods high in fiber, which contain phytic acid, may and fiber decrease magnesium decrease intestinal magnesium absorption, likely by absorption. binding magnesium to phosphate groups on phytic acid. Phosphorus Phosphorus may decrease Studies of subjects on high-phosphate diets have magnesium absorption. shown that phosphate binding to magnesium may explain decreases in intestinal magnesium absorption.

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PART III: MAGNESIUM 345 TABLE 2 Continued Substance Potential Interaction Notes Calcium High intakes of calcium may Most human studies of the effects of dietary calcium decrease magnesium on magnesium absorption have shown no effect. absorption. Calcium intakes of as much as 2,000 mg/day (in adult men) did not affect magnesium balance. However, calcium intakes in excess of 2,600 mg/day have been reported to decrease magnesium balance. Several studies have found that high sodium and calcium intake may result in increased renal magnesium excretion. Overall, at the dietary levels recommended in this report, the interaction of magnesium with calcium is not a concern. Protein Protein may affect Magnesium absorption has been shown to be lower magnesium absorption. when protein intake is less than 30 g/day. A higher protein intake may increase renal magnesium excretion, perhaps because an increased acid load increases urinary magnesium excretion. Studies in adolescents have shown improved magnesium absorption and retention when protein intakes were higher (93 vs. 43 g/day). MAGNESIUM AFFECTING OTHER SUBSTANCES Calcium Magnesium deficiency may In general, magnesium deficiency must become cause hypocalcemia. moderate to severe before symptomatic hypocalcemia develops. However, a 3-week study of dietary-induced experimental magnesium depletion in humans demonstrated that even a mild degree of magnesium depletion may result in a significant decrease in serum calcium concentration. Vitamin D Magnesium deficiency may Individuals with hypocalcemia and magnesium affect the body’s response to deficiency are resistant to pharmacological doses of vitamin D, 1,α-hydroxyvitamin D, and 1,25- pharmacological vitamin D. dihydroxyvitamin D.

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DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS 346 INADEQUATE INTAKE AND DEFICIENCY Severe magnesium depletion leads to specific biochemical abnormalities and clinical manifestations that can be easily detected. The potential effects of inad- equate magnesium intake or deficiency include the following: • Symptomatic hypocalcemia (A prominent manifestation of magnesium deficiency in humans, symptomatic hypocalcemia develops when mag- nesium deficiency becomes moderate to severe. See Table 2.) • Muscle cramps • Interference with vitamin D metabolism (see Table 2) • Neuromuscular hyperexcitability (often the initial problem cited in in- dividuals who have or are developing magnesium deficiency) • Latent tetany • Spontaneous carpal-pedal spasm • Seizures Magnesium depletion may be found in several cardiovascular and neuromus- cular diseases, malabsorption syndromes, diabetes mellitus, renal wasting syn- dromes, osteoporosis, and chronic alcoholism. Special Considerations Excessive alcohol intake: Excessive alcohol intake has been shown to cause renal magnesium wasting. Individuals who consume marginal amounts of mag- nesium and who excessively consume alcohol could be at risk for magnesium depletion. However, current evidence does not support the suggestion that magnesium deficiency causes alcoholism. Medications: A growing number of medications have been found to result in increased renal magnesium excretion. Diuretics, which are commonly used to treat hypertension, heart failure, and edema, may cause hypermagnesuria. Mothers who breastfeed multiple infants: Due to the increased milk produc- tion of a mother while breastfeeding multiple infants, increased intakes of mag- nesium during lactation, as with calcium, should be considered. The elderly: Several studies have found that elderly people have relatively low dietary intakes of magnesium. This may be due to several factors. With aging, intestinal magnesium absorption tends to decrease and urinary magnesium excretion tends to increase. Other factors include poor appetite, diminished senses of taste or smell (or both), poorly fitting dentures, and difficulty in

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PART III: MAGNESIUM 347 shopping for and preparing meals. It should also be noted that meals served by some long-term care facilities may provide less than the recommended lev- els of magnesium. EXCESS INTAKE Excess intake of magnesium from food sources is not associated with adverse effects. However, adverse effects have been observed with excessive intake from nonfood sources that are used acutely for pharmacological purposes, such as magnesium salts. They include the following: • Diarrhea (primary symptom) • Nausea • Abdominal cramps More severe adverse effects may occur with very large pharmacological doses of magnesium. They include the following: • Metabolic alkalosis • Hypokalemia • Paralytic ileus Special Considerations Impaired renal function: Individuals with impaired renal function are at greater risk of magnesium toxicity (from nonfood sources).

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PART III: MAGNESIUM 349 KEY POINTS FOR MAGNESIUM ✓ Magnesium is involved in more than 300 enzymatic processes in the body, as well as in bone health and in the maintenance of intracellular levels of potassium and calcium. ✓ The more magnesium consumed, the lower the proportion that is absorbed (and vice versa). ✓ The adult requirements for magnesium are based primarily on balance studies. The UL for adults was based on diarrhea as the critical endpoint and was derived from several studies on adults evaluating the effect of high magnesium intake from nonfood sources. The UL is based on intake from pharmacological sources of magnesium, rather than from food and water. ✓ Foods rich in magnesium include green leafy vegetables, whole grains, and nuts; population intakes of magnesium have declined with decreased intakes of these foods. ✓ Magnesium deficiency can result in hypocalcemia, muscle cramps, and seizures, as well as interfere with vitamin D metabolism. ✓ No adverse effects of magnesium intake from food sources have been demonstrated. ✓ Acute excessive intake of magnesium from nonfood sources, such as pharmacological doses of magnesium salts, can cause metabolic alkalosis, hypokalemia, and paralytic ileus.