MD's Choice: Magnesium

Major Elements

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Magnesium

Physiological Roles
Tissue Distribution of Mg
Metabolism, Absorption, and Excretion of Mg

I. Physiological Roles

Necessary for photosynthesis as a component of chlorophyll. Photosynthesis is the process by which light energy is converted into chemical energy within green plants
1. The process depends upon chlorophyll within the chloroplasts
2. Chlorophylls are Mg prophryins with Mg making up about 2.7% of their molecular weight
3. Mg stabilizes the structure so it undergoes perfectly reversible one-electron oxidations
  1. The Mg ion is oxidized in the process of the photochemical reaction
  2. Energy of the photons is captured in the form of high energy electrons
  3. The electrons are passed stepwise down an energy gradient in a structured membrane
  4. The membrane is held together with the coordinating properties of the Mg atom
  5. The energy of the electrons is used to produce ATP, which together with reduced incotinamide adenine dinucleotide (HADH), drives the formation of carbohydrate from CO₂ and H₂O
    6CO₂ + 6H₂O + 18ATP + 12HADH ® C₆H₂O₆ + 18ADP + 18Pi + 12NAD + 6O₂
Necessary for oxidative phosphorylation which releases stored energy in the mitochondrial membrane of both plant and animal cells
1. Stored energy is released by oxidative phosphorylation in the mitochondrial membrane of both plant and animal cells
2. The primary function of all mitochondria is to couple phosphorylation to oxidation
3. ATP, the main fuel of life, is produced in oxidative phosphorylation
4. All enzyme reactions known to be catalyzed by ATP have an absolute requirement for Mg
A simple list of enzymatic processes requiring Mg²⁺ ions would fill many pages. Required for activation of enzymes needed for protein synthesis
1. RNA polymerases which allow DNA to be copied by the messenger. (See section 4 first)
2. Aminoacyl transfer RNA synthetases which permit amino acid fixation on the corresponding t-RNA
3. The elongation factor of the polypeptide chain which allows the binding of aminoacyl t-RNA at the receptor site of a ribosome on m-RNA complex
4. Ribsomal peptidyltransferases which allow the formation of the peptide
Mg and growth
1. At the cellular level, divalent cations (Ca²⁺ and Mg²⁺) are required for the individual animal cells to adhere to one another
  1. The net surface charge is negative for most cells
  2. Positively charged divalent cations reduce repellent forces of these negative charges sufficient for adhesion to occur
2. At the subcellular level, sections of the chromosomes in the nucleus are held together by Ca and Mg
3. At the molecular level, Mg is necessary for protein synthesis
4. The physical integrity of the DNA helix appears to be dependent on Mg²⁺
  1. Mg²⁺ ion decreases the number DNA replication errors
  2. Mg²⁺ ion stimulates DNA repair
  3. Most of the known enzymes involved in repairing DNA lesions are dependent on Mg²⁺ at varying degrees
  4. Mg may thus by important in reducing occurrence of neoplasms
5. The physical size of the RNA aggregate is controlled by the concentration of Mg
Required by immunological process. Magnesium, immunity, and allergy: Mg is required for several steps of immunological reactions
1. Lymphoblastic transformation, a prerequisite of secretion of antibodies by lymphoblasts, requires Ca²⁺ and Mg²⁺
2. Mg is required for synthesis of proteins, immunoglobulins included
3. Antibody-induced complement activation is Mg dependent
4. The antigen-immunoglobulin-complement reaction induces degranulation of the mastocyte
  1. The degranulated mastocyte releases various substances, mainly histimine
  2. Ca²⁺ and Mg²⁺ competition appears to regulate secretion of histamine by the mastocytes
    1. Ca²⁺ ion stimulates secretion of histamine
    2. Mg²⁺ ion inhibits the secretion
5. Disorders in immunity and allergy-like symptoms have been described in Mg deficiency
Required for control of muscular contraction
1. Excitation-contraction coupling is dependent on competition between Ca²⁺ and Mg²⁺ on cellular receptors
2. The calcium pump of the sarcoplasmic reticulum is Mg-dependent
  1. Leakage of Ca from the sarcoplasmic reticulum pumps, inducing the contraction of the muscle fibrils, seems to be responsible for tetanic seizures of Mg deficiency
  2. In the cardiovascular system, Mg is active in both the vessels and on the heart (J. Am. Coll. Nutr. 5:521-532, 1986)
    1. It reduces ateriolar tone and thus decreases vascular resistance
    2. It protects the heart against arrythmia
Mg controls Na and K metabolism since Na⁺ - K⁺ATPase is Mg²⁺
Mg contributes to structural integrity of bone
In summary, functions of Mg hinge on two main properties
1. Enzyme activation
2. Competition with Ca²⁺ in excitation-secretion coupling processes

II. Tissue Distribution of Mg

Mg content of human body ranges between 300 and 400 mg/kg body weight
1. 60% is in bone
2. 29% is in muscle
3. 10% is in other soft tissues
4. 1% is in extracellular fluid
Serum Mg remains close to 1.7 mEq/liter
1. Approximately one-third is bound non-specifically to plasma proteins
2. The remaining 65%, which is ionized, appears to be the biologically active compound
3. The ratio of bound to unbound Mg is also remarkably constant
Mg content of erythrocyte varies from 4.4 and 6.0 mEq/liter
Similarity of Mg to other elements:
1. Mg shares some of the attributes of Ca in aspects of its absorption and its storage in bone
2. It is similar to K in being an important intracellular constituent
3. It resembles Na in the efficiency with which the normal kidney retains the ion when serum levels fall
4. A deficiency of Mg affects metabolism of each of the other three ions in some manner

III. Metabolism, Absorption, and Excretion of Mg

Monogastric animals
1. Site of Mg absorption. Conflicting results for site of Mg absorption have been reported depending on procedure
  1. Distal intestinal tract (J. Lab. Clin. Med. 63:71, 1964). Measured by recovery of ²⁸Mg in carcass and urine after injection in different intestinal locations
    1. Over 70% of total Mg absorption was from the colon
    2. Endogenous excretion appeared to be the reverse of absorption with most of the loss occurring in the proximal intestine
  2. Proximal small intestine. Measured by decrease in Mg content of solution perfusing different intestinal segments (Digestive Diseases 23:1, 1978)
    – Absorption of Mg was greater from the proximal intestine.
Mechanism of Mg absorption
1. Mg and other alkaline earth ions appear to share a common pathway with Ca to some extent
  1. Duodenal segments that transport Ca2+ also transport Mg2+ and Sn2+ but rates of absorption between the various ions vary in different areas of the intestine (Clin. Chem. 9:734, 1963)
  2. A common mechanism for transporting Ca and Mg across the intestinal wall and renal tubule has been suggested (Clin. Sci. 22:185, 1962)
    1. In the GI tract, Ca absorption is increased in the absence of Mg; in the absence of Ca, Mg absorption is increased
    2. In Mg deficiency, urinary excretion of Ca is decreased due to increased tubular resorption of Ca
  3. Vitamin D increases net absorption of Mg but to a lesser degree than for Ca (Clin. Sci. 57:121, 1979)
2. No single factor appears to play a dominant role in absorption of Mg as does vitamin D for Ca.
  1. Transport by solvent drag (Am. J. Physiol. 227:334. 1974).
    1. Magnitude and direction of water movement influence Mg transport in the rat intestine
    2. Substances that generate bulk water flow stimulate Mg transport
    3. Mg concentration in the water transported approaches that of simple bulk flow
3. Some Mg may diffuse passively into epithelial cells
4. Concentration of ionic Mg in digesta at the absorption site may control amount of Mg absorbed in a given time
Ruminant animals
1. Sites of absorption (p. 107 in Role of Magnesium in Animal Nutrition, 1983)
  1. The forestomach region is the primary site of Mg absorption in ruminants
  2. There is net secretion of Mg into the small intestine
  3. The colon is a secondary site of Mg absorption
2. Mg absorption from the rumen is mediated by an active transport mechanism (Res. Vet. Sci. 24:161, 1978)
  1. Net flux of Mg takes place against an electrical gradient
  2. Mg absorption is saturable at Mg concentrations above 5mM
  3. Mg absorption is markedly reduced by addition of ouabain
    1. Ouabain inhibits Na⁺ - K⁺ ATPases
    2. An ATPase may be involved in Mg transfer across rumen epithelium
Homeostatic Control of Mg
1. Fecal excretion of Mg varies inversely with Mg intake. (see section 2d on page 82)
2. The kidney efficiently retains Mg when serum levels fall
  1. Renal threshold for Mg is near 1.6 mg/dl plasma Mg (Am. J. Physiol. 222:1469, 1972)
  2. Gastrointestinal mechanisms of Mg transport are not very efficient with ordinary levels of intake
  3. There does not appear to be an efficient hormonal homeostatic mechanism for regulating serum Mg
    1. PTH mobilizes bone salts but causes little or no rise in plasma Mg in normal rats, dogs, or man
    2. Vitamin D can intensify Mg deficiency (due to a greater competition by Ca?) (Cardiovascular Med. 3:637, 1978)
    3. Calcitonin causes hypocalcemia but no significant change in serum Mg.
  4. The renal threshold is presumably the critical factor in determining the serum Mg level
Interactions with other elements
1. Calcium and Mg
  1. Mg deficiency reduces responsiveness of Ca to physiological amounts of Vitamin D (Proc. Soc. Exp. Biol. Med. 125:472, 1967)
  2. Mg deficient animals also become hypocalcemic
  3. Mg and Ca appear to share a common transport mechanism in the intestine and renal tubule. (Mg and Ca compete for absorption sites.)
    1. Ca absorption is increased in the absence of Mg
    2. Mg absorption is increased int he absence of Ca
    3. Net absorption of Ca was reduced from 61% in Mg deficient calves to 42% when supplemental Mg was given (Nature 191:181-182. 1961)
2. Potassium and Magnesium
  1. Mg deficient animals may also become hypokalemic
    1. Reduction in Na⁺ - K⁺ ATPase?
    2. Elevated aldosterone? (Proc. Soc. Exp. Biol. Med. 168:382, 1981)
      – Increased urinary K leading to decreased plasma K
      – Micropuncture analysis shows kaliuresis was due to increased K entry along the distal tubule consistent with the site of action of aldosterone
      – Aldosterone was elevated
  2. K reduces absorption of Mg by ruminants (Aust. J. Agric. Res. 27:873. 1976; J. Anim. Sci. 61:1219. 1985)
    1. Ruminal infusion of K depresses Mg absorption
    2. Infusion of K at other sites has no effect
  3. Excess K also reduces plasma Mg by mechanisms other than reduction of Mg absorption
    1. Supplemental K enhances clearance of intravenously infused Mg from plasma (J. Anim. Sci. 41:1134, 1975)
      – Urinary Mg excretion accounted for clearance of IV Mg challenge in control sheep; when sheep were fed high dietary K (4%), urinary clearance accounted for only 80% of the Mg challenge
      – K may have increased cellular uptake of Mg
3. Mg and Zn
  1. Calves fed high levels of Mg (.7 - 1.15%) excreted less Zn and retained more Zn in tissues (J. Dairy Sci. 63:457. 1980)
    1. The effect of high dietary Mg on Zn metabolism appears to be systemic in tissues
4. Tricarballylic acid, a nonmetablizable rumen fermentation product of transaconitic acid, led to depletion of Mg and other cations in rats. It could be a contributing factor in the etiology of grass tetany in ruminants. (J. Nutr. 118:183-188. 1988)

Mg requirements

Ruminants	ppm in diet DM
Beef cattle Growing & finishing Lactating cows Breeding bulls	400-1000 1800 1800
Dairy cattle Baby calves Growing heifers & bulls Dry, pregnant cows Lactating cows	700 1600 1600 2000
Sheep, all classes	400- 800

Nonruminants	ppm in diet DM
Poultry Starting chicks (0-8 wks) Growing chicks (8-18 wks) Laying hens	600 400 500
Swine Growing & finishing Breeding	400 400
Horses Growing Mature Maintenance	1000 900

Humans	Meq/kg/d	mg/kg/d
Infants	0.8-1.6	9.7-19.5
Young children	1.0	12.2
Adults Men Pregnant women	0.33-0.35 0.5	4-4.25 (280-300 mg for 70 kg) 6.1

Sources of Mg
1. Highly purified foods (sugars, starches, soft drinks, alcohol) contain negligible Mg
2. Cows milk contains a moderate amount of Mg but its high P and Ca content adversely affects Mg utilization
3. Whole grains, dried beans, and green vegetables are good sources of Mg
4. Concentrates are generally higher in Mg than are roughages
5. There is a high degree of variability in forages presumably due to soil availability
6. Legumes are generally higher in Mg than grasses
7. Supplemental Mg (MgO, Mg aspartate hydrochloride) may be necessary to maintain Mg balance on some diets
Deficiency of Mg
1. Two types of Mg deficiency occur in cattle
  1. Calves given an all-milk diet or otherwise fed insufficient Mg until body stores are depleted
  2. Grass tetany. Predominantly in lactating cows
    1. A problem in lactating cows grazing highly fertilized pasture during cool seasons
      – Cattle have relatively little readily mobilizable Mg reserves
      – Maintenance of extracellular Mg is crucial
      – Extracellular Mg is replenished primarily by absorption from the digestive tract.
      – Any interruption of Mg absorption can permit plasma Mg to fall to critically Iow levels in a short time
    2. Grass tetany usually develops before there is a material depletion of Mg stores
    3. Several factors can interrupt Mg supply
      – Low Mg content in forages
      – Depression of Mg absorption by high K content of rapidly growing early spring forage
      – Reduced solubility of forage Mg can delay absorption of Mg
  3. c. Clinical symptoms of Mg deficiency in ruminants. Symptoms of grass tetany are similar to those of Mg depletion in calves
    1. Reduced appetite
    2. Greatly increased excitability
    3. Calcification of soft tissue
    4. Convulsions, animal falls on side with legs alternately relaxed and rigidly extended
    5. Death often occurs during the convulsions
  4. Post mortem findings
    1. Pinpoint hemorrhages on surface of lung, liver and heart
    2. Inflated, hemorrhagic lungs
    3. Myocardial infarction
    4. Constriction of air passages in lungs and contraction of small blood vessels
    5. Evidence of platelet activation
Mg Excess
1. Livestock
  1. Toxicosis due to infestation of natural feedstuffs is extremely unlikely
  2. Mg is toxic when administered at high levels
  3. Signs of Mg toxicity
    1. Lethargy
    2. Disturbance in locomotion
    3. Diarrhea
    4. Reduced feed intake and performance
    5. Death
2. Humans
  1. Causes of Mg intoxication
    1. Renal insufficiency
    2. Large doses of MgSO4 administered in eclampsia
    3. Infants born to mothers who have had MgSO4 treatment for eclampsia
    4. Use of Mg-containing antacids (especially in patients with renal failure)
  2. Signs of Mg intoxication
    1. Excess Mg appears to block neuromuscular transmission due to diminution of endplate potential.
      – Hypocalcemia
      – Decreased deep tendon reflexes
      – Respiratory paralysis
      – Heart block
3. Maximum tolerable levels of Mg
  1. Poultry and swine 0.3%
  2. Cattle and sheep 0.5%

References:

Shattock, M. J., D. J. Hearse, and C. H. Try. 1987. The ionic basis of the anti-ischemic and anti-arrhythmic properties of magnesium in the heart. J. Am. Col. Nutr. 6:27-33
Flink, E. B. 1985. Magnesium deficiency in human subjects - A personal historical perspective. J. Am. Col. Nutr. 4:17-31
Standig-Lindberg, G., eta., 1987. Changes in serum magnesium concentration after strenuous exercise. J. Am. Col. Nutr. 6:35-40
Rayssaquier, y. and E. Gueux. 1986. Magnesium and lipids in cardiovascular disease. J. Am. Col. Nutr. 5:507-519
Fort, P. and F. Lifshitz. 1986. Magnesium status in children with insulin dependent diabetes mellitus. J. Am. Col. Nutr. 5:69-78
Dychner, T., D. Hallberg, E. Hultman, and P. O. Wester. 1982. Magnesium deficiency following jejunoileal bypass operation for obesity. J. Am. Col. Nutr. 1:239
Berthelot, A., and J. Esposito. 1983. Effects of dietary magnesium or the development of hypertension in the spontaneously hypertensive rat. J. Am. Col. Nutr. 2:343-353

Major Elements

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