Magnesium
Deficiency:
HUMAN NEEDS FOR
MAGNESIUM ARE NOT MET BY MOST PEOPLE
|
Mildred
S. Seelig, M.D., Master of Public Health, Master of the
American College of Nutrition,
Adjunct Professor of Nutrition, University of North
Carolina Medical Center, Chapel Hill |
The
American diet is rich in proteins, carbohydrates and fats
but it is commonly poor in magnesium (Mg). Additionally,
most supplements of vitamins and minerals, that are taken
by many to assure adequate nutrition, provide Mg in only
minimal amounts, if at all. Mg is a mineral that is
essential for health in optimal quantities, if we are to
obtain full benefit from the foods we eat and from the
supplements we take. Mg is needed by our bodies to
activate numerous enzymes that control metabolism of
carbohydrates, fats and electrolytes; to assist in the
utilization of other essential minerals, including calcium
(Ca) and to build the nucleic acids and our body’s
proteins from the amino acids provided by the proteins
found in food. Without adequate Mg, energy production
falters and proteins cannot be produced in sufficient
quantity for normal growth and development of infants,
children, adolescents and pregnant women. Mg also is
important in repair of wear and tear of everyday living,
in maintaining resistance to infection, in protecting
against cardiovascular, kidney and bone disease and in
meeting the excess needs caused by emotional or physical
stress.
On a milligram per kilogram (mg/kg) of lean body weight
basis, women have been shown to need 4.5-5 mg/kg/day and
men to need at least 6 mg/kg/day to remain in Mg balance
as determined by analysis of metabolic balance studies
done worldwide.1,2 These studies disclosed that, on
marginal intakes, there was better retention of Mg by
young women than by young men. The Food and Nutrition
Board of the National Research Council, National Academies
of Science, have long estimated that the Recommended
Dietary Allowances (RDAs) for Mg intakes (an amount
estimated as enough to prevent diseases associated with Mg
deficiency) are 300 mg/day for women and 350/day for men.3
The RDA for Mg was increased to 310-320 mg/day for women
and 400-420 mg/day for men in the 1997 edition, entitled
Dietary Reference Intakes (DRI),4 in which new dietary
categories were developed, including Tolerable Upper
Limits (UL). The UL designates supplemental amounts
estimated to result in adverse effects if habitually
exceeded. The Mg UL was limited to avoid diarrhea in
unduly vulnerable subjects. The ULs for Ca, phosphate and
vitamin D, high intakes of which interfere with Mg
utilization (see below), were increased substantially more
than was the UL for Mg.
Optimal Mg intakes are amounts that maintain normal
functioning of the body and prevent disorders treatable
with Mg supplements. Research, done throughout the world,
shows that the original RDA for Mg is not even sufficient
to assure compensation for the amount lost in excreta and
sweat, in the presence of even minor physical or mental
exertion or competition, aggravation or other stresses,
all of which increase Mg requirements5-8 (see below). Even
for adults living non-stressful, not particularly active
lives, it is not enough merely to maintain Mg balance,
which is the term used to describe the equilibrium between
Mg intake and output. The amount actually consumed from
self-selected diets, as shown in the United States9-14,
Europe15-18 and Asia19-21 is less than the RDA, and is far
less than the amount shown to be required to maintain
equilibrium in metabolic balance studies.1, 2,10,32 No one
can afford to lose more Mg than is provided by the diet.
When that happens, the person is in negative Mg balance.
This means that, in order to maintain normal vital
functions, the Mg that is already in the body that is
serving to activate enzymes, to maintain energy and normal
electrolyte levels in the cells, as well as to form
healthy |
|
structures,
is drawn upon, with the result that some tissues are
broken down to meet the demands of organs needed to
sustain life.
The higher figures for the RDA established in 1997 might
be closer to optimal amounts of Mg, being estimated as the
amounts needed to prevent damage to the body and to
maintain health. All tissues are at risk of malfunction
and/or physical injury when Mg levels are low; they
include the heart, arteries, kidneys, bones, hormones,
muscles, nerves, brain, skin and the gastrointestinal
organs. Chronic or long-term Mg deficiency is contributory
to development of many disorders and diseases.8 Treatment
of these illnesses can intensify the problem because many
medications increase Mg loss. When the deficiency is acute
and severe, it can cause seizures or rapid, irregular
heart beats (arrhythmias) that can prove fatal. Which
disorders develop will depend upon one’s hereditary
predisposition.22-24 Some families are prone to high blood
pressure and other types of cardiovascular disease, some
to kidney stones, some to bone thinning, chronic fatigue,
muscle cramping, nervousness and some types of severe,
recurrent headaches – in all of which subnormal Mg
levels have been encountered and increased Mg intakes have
proven helpful.
Positive Mg balance is achieved when the body retains some
of the Mg that is consumed, rather than eliminating an
amount equal to the amount ingested and absorbed. The
retained Mg participates in building healthy new tissue, a
state that is called anabolism. This is the condition
found in pregnant and nursing mothers, in those who have
not reached full growth and maturation and in athletes who
are developing their musculature. It is also the state of
people recovering from illness, surgery or accidental
trauma. A positive Mg balance indicates that this vital
mineral is being used in the formation of the proteins of
muscles, whether of our limbs, heart, arteries, kidneys
and hormones. Mg is also necessary to form normal bones
– to convert vitamin D to one of the hormones needed for
utilization of Ca,25-27 which is the major structural
component of bone. Less widely considered is the role of
Mg in forming the organic portion of bone (bone matrix)
that prevents brittleness and protects against fractures.
To attain positive Mg balance, its daily intake must be
optimal – adequate to meet special requirements. The
amount needed by those undergoing growth and development,
repair or participating in strenuous exercise is greater
than the amount needed by adults living sedentary lives.
Even the recently increased RDAs are unlikely to be
optimal for individuals with such special needs.
Adolescent boys and girls, especially those engaged in
athletics, can require as much as 7-10 mg/kg/day. Pregnant
women, particularly those with more than one fetus, those
who have undergone frequent pregnancies, or who themselves
have not attained full growth, have high Mg requirements
– at least 450 mg/day or possibly up to 15 mg/kg/day.29
Growing and developing infants and children are also in
need of high daily intakes of Mg.
Calcium, Phosphate and
Vitamin D
Mg intakes have fallen slightly over the twentieth century
in the United States, but the Ca/Mg dietary ratio, which
was about 2/1 in the first quarter of the century,30 has
risen and the RDAs for Ca and vitamin D (the vitamin that
increases Ca absorption) have been increased. These are
nutrients that have been shown to interfere with Mg
retention yet require Mg for their normal utilization.
Phosphate intake has also risen as a result of its
addition to processed |
foods
and soft drinks and this also interferes with Mg
absorption.31 The RDAs for Ca and phosphate are given as
1000 mg/day each in the 1997 book that raised the RDA for
Mg to a lesser degree.4 The tolerable upper level (UL) for
Ca is given as 2500 mg, for phosphate as 3500 mg and for
vitamin D as 2000 units. However, the UL for Mg
supplements is limited to 350 Mg, which, added to that in
food and water, might increase the daily Mg intake to
about 650 mg. For those accepting the upper limit as
desirable, unphysiologic Ca/Mg ratios can result. The high
tolerable upper limit for Ca, phosphate and vitamin D can
intensify Mg deficiency.
Carefully done human metabolic studies have verified that
high Ca/Mg and phosphate/Mg dietary intakes (within the
limits of usual diets and below the ULs cited by the Food
and Nutrition Board) have been shown to cause negative Mg
balance. Compilation and analysis of early extensive Mg
balance studies of normal young adults showed that at Mg
intakes below 5 mg/kg/day, negative balances of both Mg
and Ca develop when Ca intakes are not particularly
high.1, 32 On Mg intakes below 300 mg/day, Mg balances
were consistently either negative or barely in balance at
Ca intakes of 1 g/day. At 5-6 mg/kg/day of Mg, Ca intakes
below 1 g/day allowed for positive Mg balances, that Ca
intakes above 1 g/day diminished. Very high Ca intakes can
result in negative Mg balance if Mg intake is low. The Ca
balance is positive with high Ca/Mg dietary ratios, but in
such a circumstance, the Ca deposition can be in the soft
tissues such as the arteries and kidneys, as well as in
bone. High Mg intakes do not interfere with Ca retention
and improve Ca retention unless Ca intake is very low.
This is implemented by the favorable effect Mg has on the
hormones that control Ca absorption and its metabolism.
A Ca/Mg ratio of 2/1, provided by the daily Mg intake of
600 mg and a Ca intake of 1200 mg/day was considered
suitable for maintenance of health in 1935,30 on the basis
of study of the literature then available. The current RDA
allowances provide a Ca/Mg ratio of 3/1; the UL allows for
4/1 or higher ratios. Since phosphate excess intensifies
Mg loss,31 the high UL for phosphate can aggravate the
problem. Until there are definitive data as to optimal
intakes under different physiologic and pathologic
conditions, Mg intakes should be increased to not less
than 6 mg/kg/d for young adults.1,2,16
In a study of elderly men, whose dietary Mg intake was
maintained at their customary 250 mg/day and their Ca
intake was raised to 1400 mg/day, negative Mg balance
developed.33 When their Mg intake was increased to 500 mg,
Mg equilibrium was restored. Similarly, a negative Mg
balance was produced by increasing their phosphate intake
from the close to the RDA level of 975 mg/day to 1500 mg
daily – an amount that is common in the American diet
and is less than half of the tolerable UL.
An important study of 15 young women, who underwent three
consecutive 20 day balance periods, while on a diet that
provided RDA levels of Mg (265 to 305 mg), Ca (1008 to
1085 mg), RDA levels of phosphate and which provided a
Ca/Mg ratio of 3.7/1, showed that on controlled RDA
intakes, they lost about 50 mg of Mg a day.34 The authors
considered this to be an indication that not less that 6
mg/kg/day of Mg is needed by young women. They also
observed a gradual rise in serum cholesterol, despite low
dietary fat intake during the three observation periods.
That vitamin D is required for the absorption of Ca is
widely recognized, an effect that has been relied upon to
prevent rickets in children. High doses are now
recommended, along with a high dosage of Ca, to protect
against osteoporosis. Excess Vitamin D also raises blood
levels of cholesterol.35,36
High levels of fat within the intestine, whether it is
derived from fatty foods or intestinal dysfunction, such
as steatorrhea, or short bowel, directly interfere with
the absorption of both Mg and Ca by formation of
indigestible complexes of Mg and/or the Ca with the |
|
fat.37
Excess absorbed fat can lead to high blood cholesterol.
Most important are resultant high levels of low density
lipoproteincholesterol (LDL-C), which is called a “bad
fat,” because it, and the triglycerides, cause
atherosclerosis. In contrast, the high density cholesterol
(HDL-C) fraction is the “good lipid” because it
reduces fat deposition in arteries. HDL-C is low in
patients with cardiovascular disease, while the level of
LDL-C is high.
Very important is what Mg does to the ratio of HDL-C to
LDLC. The observation that Mg supplements increase the HDL-C/LDL-C
ratio in the blood of normal subjects and in patients with
high blood pressure or with coronary heart disease38-41 is
an explanation of one of the benefits of increasing Mg
uptake.
High sugar intake, high blood sugar levels common in
diabetic patients and moderate alcohol consumption cause
renal loss of Mg.42,43 Heavy alcohol drinking causes
severe Mg deficiency, not only from the renal loss, but
also as a result of poor diet and hormonal disturbances
that develop in patients with cirrhosis of the liver, a
consequence of chronic alcoholism.
Adequate protein intake is necessary for optimal Mg
retention. This was shown in adolescent girls and boys and
women on diets that had marginal supplies of Mg and
protein. Their Mg balance was improved by increasing their
protein intake from low to normal. Diets containing
sufficient Mg for growth and development (10-16 mg/kg/day)
in adolescent boys resulted in positive balances
regardless of the protein intake.44 However, very high
protein intakes have been shown to increase the risk of Mg
deficiency, when the diets were low or marginal in Mg.
This was first shown in infants with protein calorie
malnutrition, whose protein deficiency had been repaired
without correcting their Mg deficit. They developed
cardiac arrhythmias that could terminate fatally in those
not provided Mg supplementation.45 Arrhythmias,
attributable to loss of Mg, have also been reported as a
result of consuming a liquid protein diet for weight
reduction,46 an approach to obesity that resulted in what
was called “liquid protein mayhem” because it resulted
in deaths caused by ventricular arrhythmias.47
Cardiovascular, Renal, Bone
Diseases
The diseases receiving most attention as being associated
with Mg deficiency are those of the arteries and the
heart.8,22 Many experimental studies in laboratory animals
have demonstrated that Mg deficiency alone, especially in
combination with nutrients that interfere with Mg
utilization, causes cardiovascular damage resembling that
seen in diseases that afflict mankind. Studies of disease
frequency in different parts of the United States, and
throughout the world, have disclosed that poor Mg intake
from food and/or water is more prevalent in regions where
cardiovascular diseases are a greater problem than where
Mg intake is high.48 Hard water (containing predominantly
Mg) has been found to be protective. The southeast of the
United States, where the water is soft and poor in Mg, is
known as the “heart disease – kidney stone belt.” In
contrast, the north Midwestern states, which have water
supplies rich in Mg, have fewer cases of heart disease.
Since some hard waters are rich in Ca, its possibly
protective effect has also been proposed. However, studies
from Finland implicate a Ca/Mg ratio of 4/1 in the very
high death rate of middle-aged men from coronary heart
disease in that country.49 Because high Ca intake is
currently recommended to decrease the risk of
osteoporosis, it is noteworthy that the incidence of
osteoporosis is very high in Finland, despite lifelong
high Ca/Mg intake ratios.48,49 Another clue that high
Ca/Mg dietary ratios and nutrients such as vitamin D that
increase Ca absorption but intensify cardiovascular damage
of Mg deficiency is the increase in cardiovascular disease
in Japan, since their diet has |
become
more like the low Mg, high Ca American diet.20 Their
earlier low incidence of coronary heart disease was
correlated with their low Ca/Mg dietary ratio.49
Physicians have used Mg to treat patients since the first
third of the twentieth century, regarding it as a
medication, rather than a nutrient, that might protect
against manifestations of diseases that respond favorably
to its administration. Its use to manage the seizures and
high blood pressure of women with toxemia of pregnancy was
begun by 1925,50 a use predicated on the early
demonstration that experimental Mg deficiency induced
convulsions, hypertension and arterial lesions in animals.
Mg treatment has been used to control the arrhythmias
caused by digitalis treatment of congestive heart failure,
an effect that was first reported in Germany in 193551 and
in the United States in 1943.52 It is accepted treatment
in conditions in which arrhythmias are a risk (in
congestive heart failure53-55 and after cardiac
surgery56,57) and even in forms of arrhythmia resistant to
drug therapy.58 Loss of Mg caused by diuretic drugs used
to control edema or hypertension also causes side effects
which are manageable by Mg repletion. Poorly controlled
diabetic patients are another group long known to have Mg
loss59 for whom Mg administration has been helpful.
Determination of intracellular Mg and Ca levels has
provided important insights into the interrelationships of
several diseases usually considered quite separate. It has
been discovered that resistance to the effects of insulin,
previously thought to be a problem only in diabetes, is
also found in patients with other metabolic disturbances
involving abnormal Mg and Ca levels in their tissues.60-66
Among these disorders are hypertension (with and without
heart disease or diabetes), obesity (with and without
diabetes), pregnancy complicated by high blood pressure
and abnormal processes associated with aging. The
existence of insulin resistance in these different
conditions has led to the use of encompassing terms such
as: syndrome X, insulin resistance syndrome and
generalized cardiovascular-metabolic disease. Common to
them all are subnormal intracellular Mg/Ca ratios. It is
thus provocative that Mg deficiency has been directly
correlated with development of insulin resistance67 and
that Mg supplements have restored responsiveness to
insulin. The observation that healthy people, who reach
and surpass 100 years of age, have higher total body Mg
and lower Ca levels than the usual elderly person,66
suggests an intriguing possibility: might increased Mg
allay some of the deleterious processes of aging?
Stress and Neuromuscular
Disorders
Stress increases the secretion of adrenalin and
corticosteroid hormones. These stress hormones mobilize Mg
from the cells and increase its renal excretion. It is
paradoxical that Mg inadequacy increases secretion of
stress hormones5-7 – a vicious cycle. Might this be why
Type A individuals are more prone to heart attacks than
are those of a more tranquil disposition? The types of
stresses that can increase Mg requirements can be physical
(exhausting or competitive exercise, exposure to extremes
of temperature, accidental or surgical trauma) or
psychological (anger, fear, anxiety, depression, grief,
tension). In continental Europe, individuals who complain
of such psychological manifestations are often diagnosed
as having latent tetany, associated with marginal Mg
deficiency.68-70 These patients frequently suffer from
pronounced fatigue, leg cramps and recurrent headaches,
including migraine, as well as psychological problems. In
the United States, where Mg levels are not often
determined in seeking an explanation of the complaints
that often lead to psychiatric consultation, a comparable
disorder is usually diagnosed as chronic fatigue
syndrome.70 |
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Difficulties in Diagnosis
Most of the body’s Mg is within the cells, rather than
in the blood plasma or serum, and it is from analysis of
serum or plasma levels of minerals that a diagnosis of Mg
deficiency is usually made. 71 The kidneys can limit the
loss of Mg to very small amounts if plasma levels drop.
However, there can be Mg deficiency in the tissues even
when plasma levels are normal. When plasma Mg is below
what is accepted as the low limit of normal, that is a
clear indication of deficiency. Adequacy, however, is not
assured by plasma levels that remain within a normal range
of values. On request, more information can be provided on
the methods of determining Mg levels. The signs of Mg
deficiency universally recognized are convulsions and
cardiac arrhythmias, but these are signs of severe
deficiency. The early arterial lesions (of the linings of
the arteries and their muscles) are free of signs, as are
early lesions of the heart and kidneys. The neuromuscular
signs of nervousness, irritability, anxiety,
gastrointestinal symptoms are more often considered
manifestations justifying psychiatric care or
investigation of intestinal status rather than closer
attention paid to the diet. Osteoporosis, accepted as a
largely nutritional problem, is treated by increasing
mineralization (Ca and vitamin D intakes) without
attention to the fact that in Finland, where Ca intake is
high and Mg intake is low, both osteoporosis and
cardiovascular disease are serious problems. 48
Adaptation to Long-Term Low
Magnesium Intakes
The difficulty in diagnosing Mg deficiency stems from the
unreliability of plasma values and the fact that there are
few overt signs of early Mg deficiency – which affect
internal tissues that have symptom-free damage.
Furthermore, the body has the ability to maintain
equilibrium, even when levels of essential nutrients (like
Mg) in the body are subnormal. 32,72 The available
evidence indicates that it takes varying but usually
prolonged periods of time for the body to adjust to
changed Mg intakes by retaining amounts needed for optimal
functioning.
When the first analysis of Mg intakes and balances in
normal young adults32 was published in 1964,1 Mg
deficiency was suggested as a neglected factor in
vulnerability to heart disease. It was then suggested that
an explanation of the lesser risk of young women might be
their maintenance of Mg equilibrium on lower intakes. The
lower rates of cardiovascular diseases in men in the East
than the West was deemed attributable in part to higher
mg/kg/day Mg intakes in the Orient (from diets comprised
largely of soy products, vegetables and fish) than in
occidental countries. More cardiovascular disease,
however, has become a problem in countries such as Japan
and in some areas in China, where the diet has changed.
20,76-80 A high sodium intake is unquestionably a factor
in high blood pressure, but low Mg intake is contributory.
In Japan, emphasis is placed on the need, not only to
lower salt, but to increase the Mg content of the diet in
order to protect against cardiovascular
disease.20,76-78,80 Largescale American surveys and
reviews of data implicate low dietary intake and serum
levels of Mg in cardiovascular disease in the United
States.48,73-75 Fewer studies have correlated low Mg
intake with osteoporosis but the coexistence of both heart
and bone disease in conditions associated with Mg loss,
including diabetes81 and alcoholism,82 is provocative.48
This recalls the prevalence of both heart disease and
osteoporosis in Finland where Mg intake is low. 48 Also,
the elderly who eat diets rich in vegetables, which are
diets high in Mg, have greater bone density and thus are
less prone to osteoporosis, than are those with less
Mg-rich diets,83 just as they are less prone to
cardiovascular disease. |
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