Research on the Mineral Magnesium
The following research abstracts
are presented to reflect the findings of possible benefits from
minerals as a dietary supplement and nutritional supplement.
You will find more on the ionic
magnesium page.
This collection of material addresses
the direct correlation between magnesium and different diseases
and ailments.
Alcohol-related
ALCOHOL. CLIN. EXP. RES. (USA),
1994, 18/5 (1057-1068)
It is not known why alcohol ingestion
poses a risk for development of hypertension, stroke and sudden
death. Of all drugs, which result in body depletion of magnesium
(Mg), alcohol is now known to be the most notorious cause of
Mg-wasting. Recent data obtained through the use of biophysical
(and noninvasive) technology suggest that alcohol may induce
hypertension, stroke, and sudden death via its effects on intracellular
free Mg2+ ((Mg2+)(i)),
which in turn alter cellular and subcellular bioenergetics and
promote calcium ion (Ca2+) overload.
Evidence is reviewed that demonstrates that the dietary intake
of Mg modulates the hypertensive actions of alcohol. Experiments
with intact rate indicates that chronic ethanol ingestion results
in both structural and hemodynamic alterations in the microcirculation,
which, in themselves, could account for increased vascular resistance.
Chronic ethanol increases the reactivity of intact microvessels
to vasoconstrictors and results in decreased reactivity to vasodilators.
Chronic ethanol ingestion clearly results in vascular smooth
muscle cells that exhibit a progressive increase in exchangeable
and cellular Ca2+ concomitant with
a progressive reduction in Mg content. Use of 31P-NMR spectroscopy
coupled with optical-backscatter reflectance spectroscopy revealed
that acute ethanol administration to rats results in dose-dependent
deficits in phosphocreatine (PCr), the (PCr)/(ATP) ratio, intracellular
pH (pH(i)), oxyhemoglobin, and the mitochondrial level of oxidized
cytochrome oxidase aa3, concomitant with a rise in brain-blood
volume and inorganic phosphate. Temporal studies performed in
vivo, on the intact brain, indicate that (Mg2+)(i)
is depleted before any of the bioenergetic changes. Pretreatment
of animals with Mg2+ prevents ethanol
from inducing stroke and prevents all of the adverse bioenergetic
changes from taking place. Use of quantitative digital imaging
microscopy, and mag-fura-2, on single-cultured canine cerebral
vascular smooth muscle, human endothelial, and rat astrocyte
cells reveals that alcohol induces rapid concentration-dependent
depletion of (Mg2+)(i). These cellular
deficits in (Mg2+)(i) seem to precipitate
cellular and subcellular disturbances in cytoplasmic and mitochondrial
bioenergetic pathways leading to Ca2+
overload and ischemia. A role for ethanol-induced alterations
in (Mg2+)(i) should also be considered
in the well-known behavioral actions of alcohol.
EUR. J. PHARMACOL. ENVIRON. TOXICOL.
PHARMACOL. SECT. (Netherlands), 41993, 248/3 (229-236)
Acute ethanol exposure (8-570
mM) induced potent contractile responses of rings in both basilar
and middle cerebral arteries, from dogs, sheep, piglets and
baboons, in a dose-dependent manner. The contractions were reproducible
and not tachyphylactic. The middle cerebral arteries were found
to be more sensitive to ethanol than the basilar arteries. No
known pharmacological antagonist, tested, exerted any effects
on ethanol-induced contractions. No differences in responsiveness
to ethanol in canine arteries were found between male and female
animals or between the presence and the absence of endothelial
cells. Removal of extracellular Ca2+
((Ca2+)0) partially attenuated ethanol-induced
contractions, while withdrawal of extracellular Mg2+
((Mg2+)0) potentiated such contractions.
In the complete absence of (Ca2+)0,
caffeine and ethanol induced similar, transient contractions
followed by relaxation in K+-depolarized cerebral vascular tissue.
Ethanol-induced contractions were completely abolished by pretreatment
of tissues with caffeine. Our results suggest that:
(a) acute ethanol intoxication can induce direct contractions
(independent of amine, prostanoid or opioid mediation) of diverse
mammalian cerebral vascular tissues, including those from primates;
(b) these contractile responses are heterogeneous along the
cerebrovascular tree and independent of endothelial cells;
(c) in addition to a need for (Ca2+)0,
an intracellular release of Ca2+ is
needed for ethanol to induce contractions; and
(d) hypomagnesemia or Mg deficiency potentiates the contractile
effects of ethanol on brain vessels and may be a risk factor
for ethanol-related, ischemic stroke events.
Amyotrophic Lateral Sclerosis
Neurotoxicology, 1991; 615-620
Low calcium/magnesium intake
with excess amounts of aluminum and manganese are associated
with the incidence of amyotrophic lateral sclerosis (ALS) in
the Western Pacific. Two Japanese case reports of ALS showed
markedly elevated concentrations of aluminum in the CNS. In
6 other cases of ALS and 5 neurologically normal controls it
was found that aluminum concentrations in the precentral gyrus,
internal capsule, crus cerebri and spinal cord were significantly
higher in 2 ALS patients compared to the controls. Mean aluminum
concentrations in 26 different central nervous system regions
in the 2 patients were higher than controls and 4 of the ALS
cases. Magnesium concentrations in 26 central nervous system
regions were markedly reduced in the ALS cases. Calcium/magnesium
ratios were significantly increased in ALS patients. The authors
conclude that the high incidence of ALS in the Western Pacific
may be due to calcium/magnesium dismetabolism resulting in excess
deposition of aluminum.
Arrhythmia
Zeitschrift fur Kardiologie (Germany),
1996, 85/SUPPL. 6 (135-145)
The use of magnesium as an antiarrhythmic
agent in ventricular and supraventricular arrhythmias is a matter
of an increasing but still controversial discussion during recent
years. With regard to the well established importance of magnesium
in experimental studies for preserving electrical stability
and function of myocardial cells and tissue, the use of magnesium
for treating one or the other arrhythmia seems to be a valid
concept. In addition, magnesium application represents a physiologic
approach, and by this, is simple, cost-effective and safe for
the patient. However, when one reviews the available data from
controlled studies on the antiarrhythmic effects of magnesium,
there are only a few types of cardiac arrhythmias, such as torsade
de pointes, digitalis-induced ventricular arrhythmias and ventricular
arrhythmias occurring in the presence of heart failure or during
the perioperative state, in which the antiarrhythmic benefit
of magnesium has been shown and/or established. Particularly
in patients with one of these types of cardiac arrhythmias,
however, it should be realized that preventing the patient from
a magnesium deficit is the first, and the application of magnesium
the second best strategy to keep the patient free from cardiac
arrhythmias.
Japanese Circulation Journal
(Japan), 1996, 60/11 (871-875)
Magnesium affects cardiac function,
although until the recent development of a new ion selective
electrode no method existed for measuring the physiologically
active form of magnesium, free ions (iMg2+),
in the blood. We investigated the antiarrhythmic effect of magnesium
sulfate administered to critically ill patients with cardiac
arrhythmias and reduced iMg2+ as determined
using the ion-selective electrode. Eight patients with a low
iMg2+ level (less than 0.40 mmol/L)
were given intravenous magnesium sulfate (group L). Magnesium
sulfate was also administered to patients with a normal iMg2+
level (more than 0.40 mmol/L) but who did not respond to conventional
antiarrhythmic drugs (group N). Intravenous magnesium sulfate
significantly increased the iMg 2+ level in patients in group
L from 0.35plus or minus0.06 mmol/L (mean plus or minus SD)
to 0.54 plus or minus 0.09 mmol/L (p<0.01), and had an antiarrhythmic
effect in 7 of the 8 patients (88%). However, in group N patients,
intravenous magnesium sulfate had an antiarrhythmic effect in
only 1 of the 6 patients (17%) (p<0.05 vs group L). These
results suggest that intravenous magnesium sulfate may be effective
in the acute management of cardiac arrhythmias in patients with
a low serum iMg2+ level.
Clinical Cardiology (USA), 1996,
19/4 (325-331)
The aim of this review is the
utmost simplification of the cellular electrophysiologic background
of ischemia-related arrhythmias. In the acute and subacute phase
of myocardial infarction, arrhythmias can be caused by an abnormal
impulse generation, abnormal automaticity or triggered activity
caused by early or delayed after depolarizations (EAD and DAD),
or by abnormalities of impulse conduction (i.e., reentry). This
paper addresses therapeutic intervention aimed at preventing
the depolarization of 'pathologic' slow fibers, counteracting
the inward calcium (Ca) influx that takes place through the
L-type channels (Ca antagonists), or hyperpolarizing the diastolic
membrane action potential increasing potassium (K) efflux (K-
channel openers) in arrhythmias generated by an abnormal automaticity
(ectopic tachycardias or accelerated idioventricular rhythms).
If the cause of enhanced impulse generation is related to triggered
activity, and since both EAD and DAD are dependent on calcium
currents that can app ear during a delayed repolarization, the
therapeutic options are to shorten the repolarization phase
through K-channel openers or Ca antagonists, or to suppress
the inward currents directly responsible for the after depolarization
with Ca blockers. Magnesium seems to represent a reasonable
choice, as it is able to shorten the action potential duration
and to function as a Ca antagonist.
Chinese Pharmacological Bulletin
(China), 1994, 10/5 (358-362)
The effect of tauring (Taur)
alone and in combination with magnesium sulfate (MgSO4) on ischemia/reperfusion
arrhythmia was investigated. The arrhythmia as produced by coronary
artery occlusion for 10 min followed by reperfusion. In addition,
the present study also observed the effect of MgSO4 alone and
in combination with Taur on hemodynamics. The results showed
that Taur (50-mg. kg-1) and MgSO4 (25 mg. kg-1) had partly antiarrhythmic
effect. Taur (100, 150mg. kg-1) MgSO4 (50, 100mg. kg-1) had
significantly antiarrhythmic effect. Taur (50 mg. kg-1) combined
with MgSO4 (25 mg. kg-1) shortened the duration of ventricular
tachycardia (VT) more than that either drug did alone. The hypotensive
effect of MgSO4 (25 mg. kg-1) was not increased by coadministration
of Taur, but the myocardial oxygen consumption was reduced.
These findings indicate that Taur in combination with MgSO4
has more effect on reperfusion arrhythmia, and that the mechanism
of antiarrhythmic effect of Taur and MgSO4 may be involved in
the effect of defence on myocardium.
Asthma
Indian Pediatrics (India), 1997,
34/5 (389-397)
Objective: To evaluate the effectiveness
of early administration of intravenous magnesium sulfate (IV
MgSO4) in children with acute severe asthma not responding to
conventional therapy. Design: Randomized double-blind, placebo-controlled
trial. Setting: Pediatric emergency service of a large teaching
hospital. Subjects: 47 children aged between 1-12 years with
acute severe asthma showing inadequate or poor response to 3
doses of nebulized salbutamol given at an interval of 20 min
each. Intervention: The MgSO4 group received 0.2 mg/kg of 50%
MgSO4 as intravenous (IV) infusion over 35 minutes and the placebo
group received normal saline infusion in the same dose and at
the same rate. MgSO4 solution and normal saline were coded and
dispensed in identical containers. Decoding was done at the
completion of the study. All the patients received oxygen, nebulized
salbutamol, IV aminophylline and corticosteroids. Results: MgSO4
group showed early and significant improvement as compared to
placebo group in PEFR and SaO2 at 30 min and 1, 2, 3 and 7 hours
after stopping the infusion (p ranging from <0.05 to <0.01).
The clinical asthma score also showed significant improvement
in the MgSO4 group 1, 2, 3 and 11 hours after stopping the infusion
(p < 0.01). Conclusion: Addition of MgSO4 to conventional
therapy helps in achieving earlier improvement in clinical signs
and symptoms of asthma and PEFR in patients not responding to
conventional therapy alone.
Clinical and Experimental Allergy
(United Kingdom), 1997, 27/5 (546-551)
Background: Magnesium is a cation
with smooth muscle relaxant and anti- inflammatory effects and
may therefore have a role in the therapy of asthma. Several
studies have investigated the effects of intravenous magnesium
in acute or stable asthma, but little is known about the effects
of inhaled magnesium. Objective: To measure the effects of a
single inhaled nebulized dose of 180 mg magnesium sulphate on
airway reactivity to a direct-acting bronchoconstrictor (histamine)
and an indirect-acting bronchoconstrictor (adenosine monophosphate
(AMP)) in asthmatic subjects. Methods: Two separate randomized,
double blind, placebo controlled crossover studies. each involving
10 asthmatic subjects. In the histamine study, airway reactivity
to histamine was measured and lung function allowed to recover
spontaneously over 50 min before administering nebulized magnesium
sulphate or saline placebo. Airway reactivity to histamine was
then measured at 5 and 50 min. In the AMP study, a single measurement
of airway reactivity was made 5 min after magnesium or placebo.
Results: In the histamine study, the provocative dose required
to reduce FEV1 by 20% (PD20FEV1) was significantly lower after
magnesium than after placebo, by a mean (95% CI) of 1.02 (0.22-
1.82) doubling doses at 5 min (P=0.018), and 1.0 (0.3-1.7) doubling
doses at 50 min (P = 0.01). In the AMP study, PD20FEV1 was also
significantly lower at 5 min after magnesium than alter saline,
by 0.64 (0.12-1.16) doubling doses (P = 0.023), though this
difference was not statistically significant.
Chest (USA), 1997, 111/4 (858-861)
Background: Inhaled magnesium
(Mg) seemed to have a mild protective (nonbronchodilator) effect
against histamine and methacholine. Inhaled sodium metabisulfite
(MBS) causes bronchoconstriction in asthma through indirect
mechanisms that involve sensory, nerve stimulation, and it is
extensively used to study airway hyperresponsiveness. We designed
this double-blind, randomized, crossover, and placebo-controlled
study to test the effect of nebulized Mg sulfate against indirect
challenge with MBS. Methods: Ten asthmatic subjects (three male)
aged 38.8 (3.29, SEM) years came on three occasions to perform
MBS challenges 5 min after inhalation of either normal saline
solution as placebo or Mg sulfate (4 mL; 286 mOsm). Doubling
increasing concentrations of MBS were administered by continuous
nebulization at tidal breathing during 1 min starting at 0.3
to 80 mg/mL until a 20% fall in FEV1 (PC20) from post saline
solution baseline value was achieved. PC20 values were logarithmically
transformed before analysis. Results: The mean baseline FEV1
at control day was 2.52 (0.14) L and 88.46 (4.28) percentage
predicted, while the geometric mean MBS PC20 was 1.95 (1.38,
geometric SEM) mg/mL. After placebo, the geometric mean PC20
was 2.26 (1.26) mg/mL. Inhaled Mg increased significantly the
PC20 to 5.06 (1.52) mg/mL; p<0.05. Mg diminished the bronchoconstrictor
response to MBS by 1.3 doubling doses (p=0.08). Conclusions:
Inhaled Mg attenuates MBS-induced bronchoconstriction in these
asthmatic subjects. This new feature of Mg, even modest in magnitude,
emphasizes the necessity of studying the potential role of this
cation in modulating airway response.
Journal of Pharmaceutical Sciences
(USA), 1996, 85/10 (1026-1034)
Nedocromil sodium is used in
the treatment of reversible obstructive airways diseases, such
as asthma. The physicochemical, mechanical, and biological characteristics
of nedocromil sodium can be altered by its conversion to other
salt forms. In this study, three crystalline hydrates, the pentahydrate,
heptahydrate, and decahydrate, of a bivalent metal salt, nedocromil
magnesium (NM), were prepared. The relationships between these
hydrates were studied through their characterization by differential
scanning calorimetry (DSC), thermogravimetric analysis (TGA),
Karl Fischer titrimetry (KFT), hot stage microscopy (HSM), ambient
or variable temperature powder X- ray diffraction (PXRD), Fourier-transform
infrared (FTIR) spectroscopy, solid-state nuclear magnetic resonance
(SSNMR) spectroscopy, scanning electron microscopy (SEM), water
uptake at various relative humidities (RH), intrinsic dissolution
rate (IDR), and solubility measurements. The pentahydrate showed
two dehydration steps, corresponding to two binding states of
water, a more temperature-sensitive tetramer and a more stable
monomer, deduced from the crystal structure previously determined.
The heptahydrate and decahydrate each showed a dehydration step
with a minor change in slope at about 50 degrees C, which was
analyzed by derivative TGA and confirmed by DSC. HSM and variable
temperature PXRD also confirmed the thermal dehydration behavior
of the NM hydrates. The decahydrate underwent an apparently
irreversible phase transformation to the pentahydrate at 75
degrees C at an elevated water vapor pressure. The PXRD, FTIR,
and SSNMR of the decahydrate were similar to those of the heptahydrate,
suggesting that the three extra water molecules in the decahydrate
are loosely bound, but were significantly different from those
of the pentahydrate. The rank order of both IDR and solubility
in water at 25 degrees C was heptahydrate similar decahydrate
pentahydrate, corresponding to the rank order of free energy
with respect to the aqueous solution.
Ann Emerg Med (UNITED STATES)
Nov 1992, 21 (11) p1337-42
STUDY OBJECTIVE: To determine
the magnitude of the changes in serum potassium, magnesium,
and phosphate during the treatment of acute bronchospasm with
repeated doses of beta-adrenergic agonists. DESIGN: Prospective
study of a convenience sample of asthmatic patients. SETTING:
University teaching hospital emergency department. TYPE OF PARTICIPANTS:
Twenty-three patients met the inclusion criteria of age of more
than 16 years; a history of asthma or chronic obstructive pulmonary
disease; and an acute exacerbation. INTERVENTIONS: Baseline
peak expiratory flow rate and serum potassium, magnesium, and
phosphate levels were measured. Nebulized albuterol (2.5 mg)
was administered every 30 minutes until the patient was discharged
from the ED. Before each albuterol treatment, repeat serum levels
of potassium, magnesium, and phosphate were determined. MEASUREMENTS
AND MAIN RESULTS: Baseline peak expiratory flow rate averaged
188 +/- 119 L/min. Serum potassium levels decreased significantly
(P = .0001 by repeated-measures analysis of variance) from 4.10
+/- 0.468 (baseline) to 3.55 +/- 0.580 mmol/L (90 minutes) and
3.45 +/- 0.683 mmol/L (180 minutes). Potassium decreased to
less than 3.0 mmol/L in 22% of patients at some point during
the study. Magnesium decreased from 1.64 +/- 0.133 mmol/L (baseline)
to 1.48 +/- 0.184 mmol/L (90 minutes) and 1.40 +/- 0.219 mmol/L
(180 minutes) (P = .0001). Phosphate levels also decreased,
from 3.74 +/- 1.029 (baseline) to 2.84 +/- 0.957 mmol/L (90
minutes) and 2.55 +/- 0.715 mmol/L (180 minutes) (P = .0001).
CONCLUSION: Aggressive administration of nebulized albuterol
during the emergency treatment of acute bronchospasm is associated
with statistically significant decreases in serum potassium,
magnesium, and phosphate. The mechanism and clinical significance
of these findings are unknown and warrant further study.
Skotnicki AB; JabLonski MJ; MusiaL J; Swadzba
J
Kliniki Hematologii Collegium Medicum Uniwersytetu Jagiellonskiego
w Krakowie. Przegl Lek (Poland) 1997, 54 (9) p630-3
Magnesium is the fourth most abundant metal found
in the body. It plays a crucial role in numerous biological
processes. It is a natural calcium antagonist. New experimental
data suggest that Mg+2 influences a variety of lung structures.
Intracellular Mg+2 is thought to modulate smooth muscle contractions
and it is known to have a direct effect on calcium uptake, resulting
in smooth muscle relaxation. Magnesium has been forgotten cation
from the therapeutical point of view, but now several clinical
reports point to the salutary actions of Mg+2 in various lung
diseases. Many reports suggests that magnesium sulfate and aspartate
has certainly a role as an adjunct to traditional therapy in
asthma and asthma-like conditions and have been helpful in the
treatment of acute exacerbations of asthma. (45 Refs.)
Attention Deficit Disorder
Psychiatry Res (IRELAND) Nov
1994, 54 (2) p199-210
Levels of calcium in plasma,
red blood cells, and mononuclear blood cells, levels of calcium
in plasma, and the plasma calcium-to-magnesium ratio were measured
at baseline and after 3 weeks of each drug phase of a double-blind,
placebo-controlled study of methylphenidate and dextroamphetamine
in hyperactive boys. Levels of magnesium in plasma were significantly
higher after 3 weeks of dextroamphetamine treatment, and the
calcium-to-magnesium ratio was significantly lower after 3 weeks
of either drug compared with the baseline or placebo condition.
There was no change in magnesium levels in red blood cells or
mononuclear blood cells. These measures were obtained 30 minutes
before the morning dose and at 9 a.m., 9:30 a.m., 10:30 a.m.,
11:00 a.m., and noon on the last day of each 3-week phase. Analysis
of variance revealed a drug effect on plasma magnesium and on
the calcium-to-magnesium ratio but no drug x time interaction.
Although these changes were not correlated with the time course
of acute symptomatic response to stimulant therapy, the decrease
in the ratio may be relevant to side effects and treatment resistance
associated with stimulant use.
Psychiatr Pol (POLAND) May-Jun
1994, 28 (3) p345-53
The magnesium, zinc, copper,
iron and calcium level of plasma, erythrocytes, urine and hair
in 50 children aged from 4 to 13 years with hyperactivity, were
examined by AAS. The average concentration of all trace elements
was lower compared with the control group-healthy children from
Szczecin. The highest deficit was noted in hair. Our results
show that it is necessary to supplement trace elements in children
with hyperactivity.
Wiad Lek (POLAND) Feb 1993, 46
(3-4) p120-2
In 142 girls and 107 boys aged
5-15 years serum magnesium level was determined by the colorimetric
method. Decreased values were found in 24 children including
7 boys and 17 girls. In 21 of them neurotic reactions or concentration
disturbances were observed.
Cerebral
J. CARDIOVASC. PHARMACOL. (USA),
1994, 23/6 (1004-1010)
Mg2+
influences the response of cerebral arteries to several agonists,
but until now its effects on endothelin-1 (ET-1) had not been
studied. We recorded and compared the responses of goat cerebrovascular
bed to ET-1 and 5-hydroxytryptamine (5-HT) during various Mg2+
treatments. We performed experiments in vitro by recording isometric
tension in isolated goat middle cerebral arteries and in vivo
by recording cerebral blood flow (CBF) and other physiologic
parameters in conscious goats. Cumulative addition of ET-1 (10-101-3
x 10-8M) and 5-HT (10-9-10-5M) contracted cerebral arteries
concentration dependently in bath media containing 0 (Mg2+
free medium), 1 (control), and 10 mM Mg2+,
but the influence of Mg2+ was different:
Mg2+ deprivation increased sensitivity
(EC50) and Mg2+ overload reduced contractility
(E(max)) of cerebral arteries to 5-HT, whereas the ET-1 response
did not change in these conditions. Cumulative addition of Mg2+
(10-4-3 x 10-2M) at the active tone induced by ET-1 (10-9M)
and 5-HT (10-5M) elicited concentration-dependent relaxations
of cerebral arteries, but the relaxant response was lower at
the ET-1 precontraction. Infusions of ET-1 (0.1 nmol/min) and
5-HT (10 microg/min) directly into the cerebroarterial supply
of the unanesthetized goats elicited a sustained decrease in
CBF and an increase in cerebral vascular resistance. Magnesium
sulfate, administered as increasing doses (10-300 mg) in the
same way increased CBF and decreased cerebral vascular resistance,
although this effect was less on ET-1-induced than on 5-HT-induced
cerebral vasoconstriction. When infused intravenously (i.v.;
3 g/15 min), magnesium sulfate had no effect on the ET-1-induced
cerebral vasoconstriction, but increased 5-HT-reduced CBF. ET-1
is a relatively Mg2+-resistant contractile
stimulus in the cerebrovascular bed. This should be taken into
account in consideration of the therapeutic potential of Mg2+
in cerebrovascular disorders in which ET-1 might be involved.
Constipation
Arzneimittelforschung (GERMANY)
Mar 1996, 46 (3) p302-6
Since in vitro experiments had
excluded interactions between Fe-gluconate (Fe-gluc) and magnesium-L-aspartate
hydrochloride (MAH) in aqueous solutions the present in vivo
studies seemed to be justified. Animal studies: Rats were kept
on magnesium-(Mg)- and iron-(Fe)- sufficient and deficient diets.
The intragastral administration of Fe-gluc significantly increased
plasma Fe after 3 h, either given alone, or in combination with
MAH (inducing hypermagnesemia). Same results were obtained when
fortified diets were offered to Fe/Mg-deficient animals. Human
studies: The combination of Fe-gluc (2 x 50 mg Fe per day, per
os) plus MAH (2 x 7.5 mmol Mg per day, p.o.) was well tolerated
by healthy volunteers. Single dose experiments revealed that
Fe-gluc alone and in combination with MAH increased plasma Fe
levels during 3 h to the same extent. Two groups of pregnant
women with moderately reduced hemoglobin levels either received
Fe-gluc (out-patients) or its combination with MAH (at least
temporarily hospitalised because of preterm labor). Treatments
were well tolerated. Hemoglobin levels did not further decrease,
as expected without Fe supplements, during the course of pregnancy,
thus indicating the therapeutic availability of the electrolytes
in both study groups. Progesterone-induced constipation is frequently
observed during pregnancy; hence stool softening reported by
50% of the women receiving Fe-gluc plus MAH (versus 33% in the
Fe-gluc group) can be regarded as desirable effect. It is concluded
that MAH does not interfere with the enteral absorption of Fe-gluc
when both electrolytes are orally administered together. Taking
both electrolytes together instead of 2 to 3 h apart from each
other, as actually recommended, means a less complicated dosage
regimen and probably improves compliance.
J Int Med Res (ENGLAND) Sep-Oct
1989, 17 (5) p442-54
In a crossover study the effects
of magnesium hydroxide on serum lipids, carbohydrates, vitamins
A and E, uric acid and whole blood minerals were compared with
those of a bulk laxative containing plantago rind and sorbitol
in 64 constipated, elderly long-stay patients, 55 of whom were
receiving diuretics. Hypomagnesaemia occurred in 11 (17%) patients
after bulk laxative and in two (2%) patients after magnesium
hydroxide treatment. There was a slight reduction in low values
of high-density lipoprotein cholesterol and high values of triglycerides
after magnesium hydroxide treatment. There were no significant
differences in plasma lipids, whole blood minerals or vitamins
A and E using either laxative. Negative correlations were found
between the increase in serum concentrations of magnesium and
glycosylated haemoglobin A1 (P less than 0.02) and the serum
level of uric acid (P less than 0.01). These results suggest
that the long-term effects of magnesium hydroxide and bulk laxative
on the absorption of nutrients may not be significantly different.
Magnesium hydroxide, however, may have beneficial effects on
lipid disorders, impaired glucose tolerance and hyperuricaemia
in magnesium deficiency due to diuretics and thus may be a favourable
laxative for use in bedridden geriatric patients receiving diuretics.
Diabetes Mellitus
Magnesium (SWITZERLAND) 1984,
3 (4-6) p315-23
Diabetes mellitus is the most
common pathological state in which secondary magnesium deficiency
occurs. Magnesium metabolism abnormalities vary according to
the multiple clinical forms of diabetes: plasma magnesium is
more often decreased than red blood cell magnesium. Plasma Mg
levels are correlated mainly with the severity of the diabetic
state, glucose disposal and endogenous insulin secretion. Various
mechanisms are involved in the induction of Mg depletion in
diabetes mellitus, i.e. insulin and epinephrine secretion, modifications
of the vitamin D metabolism, decrease of blood P, vitamin B6
and taurine levels, increase of vitamin B5, C and glutathione
turnover, treatment with high levels of insulin and biguanides.
K depletion in diabetes mellitus is well known. Some of its
mechanisms are concomitant to those of Mg depletion. But their
hierarchic importance is not the same: i.e., insulin hyposecretion
is more important versus K+ than versus Mg2+.
Insulin increases the cellular inflow of K+ more than that of
Mg2+ because there is more free K+
(87%) than Mg2+ (30%) in the cell.
The consequences of the double Mg-K depletion are either antagonistic:
i.e. versus insulin secretion (increased by K+, decreased by
Mg2+) or agonistic i.e. on the membrane:
(i.e. Na+K+ATPase), tolerance of glucose oral load, renal disturbances.
The real importance of these disorders in the diabetic condition
is still poorly understood. Retinopathy and microangiopathy
are correlated with the drop of plasma and red blood cell Mg.
K deficiency increases the noxious cardiorenal effects of Mg
deficiency. The treatment should primarily insure diabetic control.
THERAPIE (France), 1994, 49/1
(1-7)
The interrelationships between
magnesium and carbohydrate metabolism have regained considerable
interest over the last few years. Insulin secretion requires
magnesium: magnesium deficiency results in impaired insulin
secretion while magnesium replacement restores insulin secretion.
Furthermore, experimental magnesium deficiency reduces the tissues
sensitivity to insulin. Subclinical magnesium deficiency is
common in diabetes. It results from both insufficient magnesium
intakes and increase magnesium losses, particularly in the urine.
In type 2, or non-insulin-dependent, diabetes mellitus, magnesium
deficiency seems to be associated with insulin resistance. Furthermore,
it may participate in the pathogenesis of diabetes complications
and may contribute to the increased risk of sudden death associated
with diabetes. Some studies suggest that magnesium deficiency
may play a role in spontaneous abortion of diabetic women, in
fetal malformations and in the pathogenesis of neonatal hypocalcemia
of the infants of diabetic mothers. Administration of magnesium
salts to patients with type 2 diabetes tend to reduce insulin
resistance. Long-term studies are needed before recommending
systematic magnesium supplementation to type 2 diabetic patients
with subclinical magnesium deficiency.
Endocrinology and Metabolism
Clinics of North America (USA), 1995, 24/3
Magnesium depletion is more common
than previously thought. It seems to be especially prevalent
in patients with diabetes mellitus. It is usually caused by
losses from the kidney or gastrointestinal tract. A patient
with magnesium depletion may present with neuromuscular symptoms,
hypokalemia, hypocalcemia, or cardiovascular complication. Physicians
should maintain a high index of suspicion for magnesium depletion
in patients at high risk and should implement therapy early.
DIABETOLOGIA (Germany, Federal
Republic of), 1990, 33/9 (511-514)
Magnesium is an important ion
in all living cells being a cofactor of many enzymes, especially
those utilising high energy phosphate bounds. The relationship
between insulin and magnesium has been recently studied. In
particular it has been shown that magnesium plays the role of
a second messenger for insulin action; on the other hand, insulin
itself has been demonstrated to be an important regulatory factor
of intracellular magnesium accumulation. Conditions associated
with insulin resistance, such as hypertension or aging, are
also associated with low intracellular magnesium contents. In
diabetes mellitus, it is suggested that low intracellular magnesium
levels result from both increased urinary losses and insulin
resistance. The extent to which such a low intracellular magnesium
content contributes to the development of macro- and microangiopathy
remains to be established. A reduced intracellular magnesium
content might contribute to the impaired insulin response and
action which occurs in Type 2 (non-insulin-dependent) diabetes
mellitus. Chronic magnesium supplementation can contribute to
an improvement in both islet Beta-cell response and insulin
action in non-insulin-dependent diabetes subjects.
Med Hypotheses. 1984 Feb. 13(2).
P 139-51
Available evidence--some well-documented,
some only preliminary--suggests that properly-designed nutritional
insurance supplementation may have particular value in diabetes.
Comprehensive micronutrient supplementation providing ample
doses of antioxidants, yeast-chromium, magnesium, zinc, pyridoxine,
gamma-linolenic acid, and carnitine, may aid glucose tolerance,
stimulate immune defenses, and promote wound healing, while
reducing the risk and severity of some of the secondary complications
of diabetes. Refs: 125.
Heart-related
Clin Chem (UNITED STATES) Nov
1980, 26 (12) p1662-5
Atomic absorption spectrometry
was used to measure magnesium, calcium, and sodium, and emission
spectrometry to measure potassium, in myocardium (left and right
ventricles) of 26 control subjects who died of acute trauma.
Results were expressed in mumol/g of proteins. Mg/Ca and K/Na
ratios were also determined. The same measurements were made
in 24 patients who died from acute myocardial infarction. Samples
were also taken from the necrotic area. Mg/Ca and K/Na ratios
were significantly higher in the left ventricle of both populations,
thus providing evidence of anatomical and physiological differences
between the two ventricles. As a result of cytolysis and anoxia,
the Mg/Ca ratio was very significantly inverted, and the K/Na
ratio very significantly smaller, In these clinical conditions
arrhythmias could certainly be considered likely, and there
is reason to believe that magnesium depletion may be a cause
of arrhythmias.
Ann Thorac Surg (UNITED STATES)
Apr 1995, 59 (4) p921-7
Hypomagnesemia and depletion
of the body's magnesium stores is known to be associated with
an increased incidence of both cardiac arrhythmias and neurological
irritability. In a two-part prospective study we have evaluated
whether magnesium deficiency is a significant occurrence in
children treated in the intensive care unit after open heart
operations, and subsequently have sought to identify how intraoperative
metabolic changes were related to the resultant findings. In
41 children studied after operation the plasma magnesium concentration
showed a significant decrease from 0.92 mmol/L (10th to 90th
centile, 0.71 to 1.15 mmol/L) immediately after operation to
0.77 mmol/L (0.65 to 0.91 mmol/L) on the following morning.
The subsequent change in grouped values was not significant
but 14 (34.2%) and 7 (17.1%) possessed values of less than 0.7
mmol/L and 0.6 mmol/L, respectively. The occurrence of cardiac
arrhythmias was not statistically related to the occurrence
of hypomagnesemia. In 21 children perioperative changes in extracellular
and tissue magnesium, potassium, and calcium content were measured.
It was found that hemodilution with a prime low in magnesium
caused a reduction from a median of 0.81 mmol/L to 0.61 mmol/L
(p < 0.01). Plasma potassium level, however, was elevated
from 3.7 mmol/L to 4.15 mmol/L (p < 0.05) and the ionized
calcium content from 1.17 mmol/L (1.07 to 1.25 mmol/L) to 1.49
mmol/L (1.25 to 2.56 mmol/L) (p = 0.0009). The myocardial content
of magnesium did not change significantly but skeletal muscle
content was depleted from 6.75 mumol/g (2.85 to 8.35 mumol/g)
to 5.65 mumol/g (2.45 to 7.2 mumol/g) (p < 0.01)
CARDIOVASC. DRUGS THER. (USA),
1991, 5/4 (677-680)
The possibility that a magnesium
deficiency might be the underlying cause of vasospastic angina
(VA) and the efficacy of Mg administration in its treatment
were studied. Subjects included 15 patients with VA and 18 healthy
subjects as the control group. The erythrocyte Mg content was
measured by atomic absorption, and serum Mg was measured by
conventional chemical assay. The efficacy of Mg administration
was studied in seven patients with VA. The results were as follows:
(a) The mean erythrocyte Mg content was less in the group with
frequent episodes of angina (1.59 plus or minus 0.11 mg/dl)
than in the group without angina (2.11 plus or minus 0.38 mg/dl,
p < 0.01) and in the control group (2.22 plus or minus 0.29
mg/dl, p < 0.01). There was no significant difference between
the control group and patients of each group with respect to
serum Mg. (b) Coronary arterial spasm was induced by ergonovine
maleate in seven patients and was completely inhibited by the
administration of Mg sulfate (40-80 mEq, hourly) in six of these
patients; in the remaining patient neither obvious ST change
nor chest pain occurred. Thus, it was concluded that the measurement
of erythrocyte Mg content is useful to determine how easily
vasospasm might occur in VA and that the administration of Mg
might be developed as a new therapy for spasm associated with
a low erythrocyte Mg content.
CLIN. CARDIOL. (USA), 1990, 13/9
(663-665)
A 51-year-old man was diagnosed
as having variant angina by documentation of typical ST elevation
during anginal attack and also by showing coronary arterial
spasm (#2 and #12) during hyperventilation on coronary arteriography.
Large quantities of calcium blocking agents and nitrates could
not improve his symptoms. Lack of intracellular magnesium was
suspected from a daily excretion of urine magnesium (5.3 mEq)
and magnesium tolerance test (56.7%). After hourly infusion
of magnesium sulfate (80 mEq), coronary spasm could not be induced
by ergonovine.
S. AFR. MED. J. (SOUTH AFRICA),
1983, 64/18 (697-698)
Magnesium deficiency may result
from reduced dietary intake of the ion increased losses in sweat,
urine or faeces. Stress potentiates magnesium deficiency, and
an increased incidence of sudden death associated with ischaemic
heart disease is found in some areas in which soil and drinking
water lack magnesium. Furthermore, it has been demonstrated
experimentally that reduction of the plasma magnesium level
is associated with arterial spasm. Careful studies are required
to assess the clinical importance of magnesium and the benefits
of magnesium supplementation in man.
SCIENCE (USA), 1980, 208/4440
(198-200)
Isolated coronary arteries from
dogs were incubated in Krebs-Ringer bicarbonate solution and
exposed to normal, high, and low concentrations of magnesium
in the medium. Sudden withdrawal of magnesium from the medium
increased whereas high concentrations of magnesium decreased
the basal tension of the arteries. The absence of magnesium
in the medium significantly potentiated the contractile responses
of both small and large coronary arteries to norepinephrine,
acetylcholine, serotonin, angiotensin, and potassium. These
data support the hypothesis that magnesium deficiency, associated
with sudden death ischemic heart disease, produces coronary
arterial spasm.
HYPERTENSION (USA), 1993, 21/6
II (1024-1029)
Evidence suggests that magnesium
deficiency may play an important role in cardiovascular disease.
In this study, we evaluated the effects of a magnesium infusion
and dietary-induced isolated magnesium deficiency on the production
of thromboxane and on angiotensin II-mediated aldosterone synthesis
in normal human subjects. Because insulin resistance may be
associated with altered blood pressure, we also measured insulin
sensitivity using an intravenous glucose tolerance test with
minimal model analysis in six subjects. The magnesium infusion
reduced urinary thromboxane concentration and angiotensin II-induced
plasma aldosterone levels. The low magnesium diet reduced both
serum magnesium and intracellular free magnesium in red blood
cells as determined by nuclear magnetic resonance (186plus or
minus10 (SEM) to 127plus or minus9 mM, p<0.01). Urinary thromboxane
concentration measured by radioimmunoassay increased after magnesium
deficiency. Similarly, angiotensin II-induced plasma aldosterone
concentration increased after magnesium deficiency. Analysis
showed that all subjects studied had a decrease in insulin sensitivity
after magnesium deficiency (3.69plus or minus0.6 to 2.75plus
or minus0.5 min- 1 per microunit per milliliterx10-4, p<0.03).
We conclude that dietary- induced magnesium deficiency
1) increases thromboxane urinary
concentration and
2) enhances angiotensin-induced
aldosterone synthesis. These effects are associated with a decrease
in insulin action, suggesting that magnesium deficiency may
be a common factor associated with insulin resistance and vascular
disease.
CAN. J. PHYSIOL. PHARMACOL. (CANADA),
1987, 65/4 (729-745)
Contractility of all types of
invertebrate muscle is dependent upon the actions and interactions
of two divalent cations, viz., calcium (Ca2+) and
magnesium (Mg2+) ions . The data presented and reviewed
herein contrast the actions of several organic Ca2+
channel blockers with the natural, physiologic (inorganic) Ca2+
antagonist, Mg2+,on microvascular
and macrovascular smooth muscles. Both direct in vivo studies
on microscopic arteriolar and venular smooth muscles and in
vitro studies on different types of blood vessels are presented.
It is clear from the studies done so far that of all Ca2+
antagonists examined, only Mg2+ has
the capability to inhibit myogenic, basal, and hormonal-induced
vascular tone in all types of vascular smooth muscle. Data obtained
with verapamil, nimopidine, nitrendipine, and nisoldipine on
the microvasculature are suggestive of the probability that
a heterogeneity of Ca2+ channels,
and of Ca2+ binding sites, exists
in different microvascular smooth muscles; although some appear
to be voltage operated and others, receptor operated, they are
probably heterogeneous in composition from one vascular region
to another. Mg2+ appears to act on
voltage-, receptor-, and leak-operated membrane channels in
vascular smooth muscle. The organic Ca2+
channel blockers do not have this uniform capability; they demonstrate
selectivity when compared with Mg2+.
Mg2+ appears to be a special kind
of Ca2+ channel antagonist in vascular
smooth muscle. At vascular membranes it can
(i) block Ca2+ entry and exit,
(ii) lower peripheral and cerebral vascular resistance
(iii) relieve cerebral, coronary, and peripheral vasospasm,
and
(iv) lower arterial blood pressure.
At micromolar concentrations (i.e., 10-100 muM), Mg2+
can cause significant vasodilatation of intact arterioles and
venules in all regional vasculatures so far examined. Although
Mg2+ is three to five orders of magnitude
less potent than the organic Ca2+
channel blockers, it possesses unique and potentially useful
Ca2+ antagonistic properties.
J. NUTR. MED. (United Kingdom),
1994, 4/2 (169-177)
Magnesium sulphate (MgSO4) in
a 50% solution was injected initially intramuscularly and later
intravenously into patients with peripheral vascular disease
(including gangrene, claudication, leg ulcers and thrombophlebitis),
angina, acute myocardial infarction (AMI), non-haemorrhagic
cerebral vascular disease and congestive cardiac failure. A
powerful vasodilator effect with marked flushing was noted after
intravenous (IV) injection of 4-12 mmol of magnesium (Mg) and
excellent therapeutic results were noted in all forms of arterial
disease. This technique of rapidly securing very high initial
blood levels of MgSO4 produces results in arterial disease which
cannot be equaled by oral vasodilators or intramuscular (IM)
or IV infusion therapy. It is suggested that the most important
action of MgSO4 in AMI is to open up collateral circulation
and relieve ischaemia thus reducing infarct size and mortality
rates. Prophylactic use of MgSO4 and its effect on serum lipid,
fibrinogen, urea and creatinine levels are discussed.
Nippon Rinsho (JAPAN) Jan 1996,
54 (1) p59-66
It is known that the peroxidation
of LDL is a trigger for developing arteriosclerosis. The oxidized
LDL is produced by either oxidative stress or a few oxidants.
Selenium decreased in serum and some organs of stroke-prone
spontaneously hypertensive rats (SHRSP), which is a cofactor
of glutamine peroxidase. Serum magnesium decreased in patients
with diabetes mellitus, with ischemic heart disease, with essential
hypertension and with cerebral vascular lesions. Calcium to
magnesium ratio was higher in some organs of SHRSP as compared
to Wistar Kyoto rats (WKY). These changes accelerated vascular
lesions in SHRSP. (21 Refs.)
HIV
Journal of Acquired Immune Deficiency
Syndromes and Human Retrovirology ( USA), 1996, 12/1 (75-83)
There is compelling evidence
that micronutrients can profoundly affect immunity. We surveyed
vitamin supplement use and circulating concentrations of 22
nutrients and glutathione in 64 HIV-1 seropositive men and women
and 33 seronegative controls participating in a study of heterosexual
HIV-1 transmission. We assayed antioxidants (vitamins A, C,
and E; total carotenes), vitamins B6 and B12, folate, thiamin,
niacin, biotin, riboflavin, pantothenic acid, free and total
choline and carnitine, biopterin, inositol, copper, zinc, selenium,
and magnesium, HIV-infected patients had lower mean circulating
concentrations of magnesium (p < 0.0001), total carotenes
(p = 0.009), total choline (p = 0.002), and glutathione (p =
0.045), and higher concentrations of niacin (p < 0.0001)
than controls. Fifty-nine percent of HIV+ patients had low concentrations
of magnesium, compared with 9% of controls (p < 0.0001).
These abnormal concentrations were unrelated to stage of disease.
Participants who took vitamin supplements had consistently fewer
low concentrations of antioxidants, across HIV infection status
and disease stage strata (p = 0.0006). Nevertheless, 29% of
the HIV+ patients taking supplemental vitamins had subnormal
levels of one or more antioxidants. The frequent occurrence
of abnormal micronutrient nutriture, as found in these HIV+
subjects, may contribute to disease pathogenesis. The low magnesium
concentrations may be particularly relevant to HIV-related symptoms
of fatigue, lethargy, and impaired mentation.
Hypertension
Am J Clin Nutr (UNITED STATES)
Feb 1987, 45 (2) p469-75
Associations between blood pressure
and intakes of 61 dietary variables assessed by 24-h recall
method were investigated in 615 men of Japanese ancestry living
in Hawaii who had no history of cardiovascular disease or treated
hypertension. Magnesium, calcium, phosphorus, potassium, fiber,
vegetable protein, starch, Vitamin-C, and vitamin D intakes
were significant variables that showed inverse associations
with blood pressure in univariate and a multivariate analyses.
Magnesium had the strongest association with blood pressure,
which supports recent interest in its relation to blood pressure.
Nevertheless, it was not possible to separate the effect of
magnesium from that of other variables because of the problem
of high intercorrelation among many nutrients. While recommendations
based upon cross-sectional studies must be viewed cautiously,
these results suggest that foods such as vegetables, fruits,
whole grains, and low-fat dairy items are major sources of nutrients
that may be protective against hypertension.
Am J Hypertens (UNITED STATES)
Mar 1997, 10 (3) p346-55
Magnesium is one of the most
abundant ions present in living cells and its plasma concentration
is remarkably constant in healthy subjects. Plasma and intracellular
magnesium concentrations are tightly regulated by several factors.
Among them, insulin seems to be one of the most important. In
fact, in vitro and in vivo studies have demonstrated that insulin
may modulate the shift of magnesium from extracellular to intracellular
space. Intracellular magnesium concentration has also been shown
to be effective on modulating insulin action (mainly oxidative
glucose metabolism), offset calcium-related excitation-contraction
coupling, and decrease smooth cell responsiveness to depolarizing
stimuli, by stimulating Ca2+-dependent
K+ channels. A poor intracellular magnesium concentration, as
found in non-insulin-dependent diabetes mellitus (NIDDM) and
in hypertensive (HP) patients, may result in a defective tyrosine-kinase
activity at the insulin receptor level and exaggerated intracellular
calcium concentration. Both events are responsible for the impairment
in insulin action and a worsening of insulin resistance in non-insulin-dependent
diabetic and hypertensive patients. By contrast, in NIDDM patients
daily magnesium administration, restoring a more appropriate
intracellular magnesium concentration, contributes to improve
insulin-mediated glucose uptake. Similarly, in HP patients magnesium
administration may be useful in decreasing arterial blood pressure
and improving insulin-mediated glucose uptake. The benefits
deriving from daily magnesium supplementation in NIDDM and HP
patients are further supported by epidemiological studies showing
that high daily magnesium intake to be predictive of a lower
incidence of NIDDM and HP. In conclusion, a growing body of
studies suggest that intracellular magnesium may play a key
role on modulating insulin-mediated glucose uptake and vascular
tone. We further suggest that a reduced intracellular magnesium
concentration might be the missing link helping to explain the
epidemiological association between NIDDM and hypertension.
(74 Refs.)
Clin Exp Hypertens (UNITED STATES)
May 1994
The effects of dietary magnesium
(Mg) supplementation on intralymphocytic free Ca2+
([Ca2+]i) and Mg2+
([Mg2+]i) were examined in the stroke-prone
spontaneously hypertensive rats (SHRSP) at the age of 10 weeks.
After 40 day Mg supplementation (0.8% Mg in the diet), systolic
blood pressure (SBP) was significantly lower in Mg supplemented
group (Mg group) than the control group (0.2% Mg). [Ca2+]i
was significantly lower and [Mg2+]i
was significantly higher in Mg group than in the control group.
Further, [Ca2+]i was positively and
[Mg2+]i was negatively correlated
with SBP. These results suggest that dietary Mg supplementation
modifies [Ca2+]i and [Mg2+]i,
and modulates the development of hypertension.
Kidney stones
Nederlands Tijschrift voor de
Klinische Chemie (Netherlands), 1996, 21/1
Experiences are described at
a kidney stone clinic which was established as part of the Department
of Clinical Biochemistry ten years ago. During this period,
the investigational protocol has changed from an in-patient
to an out-patient scheme. The most important metabolic abnormalities
among calcium oxalate kidney stone formers were hypercalciuria,
hypernatriuria, hyperuricosuria, increased blood urate, decreased
blood phosphate and hyperphosphaturia with decreased renal phosphate
threshold. These abnormalities were found in the majority of
patients. Oxalate output was, however, increased in less than
50 percent of the patients. The effectivity of thiazides, allopurinol,
magnesium and phosphate supplementation was tested, and it was
concluded that
(a) the effect of thiazides was significant, but calciuria normalized
only in a few cases,
(b) the withdrawal of allopurinol led to a significant increase
of urate parameters only in patients without a low-purine diet,
(c) a sufficient dose of magnesium and phosphate is necessary
to achieve a therapeutic effect.
PRESSE MED. (FRANCE), 1987, 16/1
(25-27)
The inhibitory effect of magnesium
on the first stages of renal calcium stone formation is modest
in vitro and more pronounced in experimental in vivo studies.
Magnesium deficiency has not yet been convincingly demonstrated
in man. However, urinary magnesium concentrations are abnormally
low in relation to urinary calcium concentrations in more than
25% of patients with kidney stones. A supplementary magnesium
intake corrects this abnormality and prevents the recurrence
of stones. Magnesium seems to be as effective against stone
formation as diuretics. The modalities of magnesium therapy
still have to be determined and its results confirmed. Magnesium,
possibly added to drinking water, may well play a role in the
primary prevention of renal calcium stones.
KLIN. WOCHENSCHR. (Germany, Federal
Republic of), 1988, 66/3 (87-91)
An increased frequency of kidney
stone formation is reported in patients with inflammatory bowel
disease. In order to investigate its pathogenesis, the concentrations
of factors known to enhance calcium oxalate stone formation
(oxalate, calcium, uric acid) as well as of inhibitory factors
for nephrolithiasis (magnesium, citrate) were determined in
the urine of 86 patients with Crohn's disease and compared with
those of 53 metabolically healthy controls. Six patients with
Crohn's disease already had experienced calcium oxalate nephrolithiasis.
Patients with Crohn's disease had significantly higher urinary
oxalate and lower magnesium and citrate concentrations. Among
all patients magnesium and citrate were significantly lower
in those with a positive history of kidney stones. Our results
demonstrate that the increased propensity for renal stone formation
in patients with Crohn's disease is a result not only of increased
urinary oxalate, but also of decreased urinary magnesium and
citrate concentrations.
J. UROL. (BALTIMORE) (USA), 1986,
136/1 (181-183)
Different irrigating solutions
are used clinically to dissolve uric acid, cystine and struvite
stones. These studies were undertaken to assess the toxicity
to the rabbit bladder epithelium of several commonly used formulations.
Test solutions were infused antegrade through a left ureterotomy
overnight. Bladders were removed and routine histological sections
made. A pH 7.6 solution of NaHCO3 appeared harmless.
The same solution with two percent acetylcysteine produced slight
injury. All pH solutions caused significant damage to the urothelium.
Hemiacidrin, which contains magnesium, produced less danger
than did other pH 4 solutions without that cation. Our data
tend to support Suby's conclusions that addition of magnesium
reduces urothelial injury even though the presence of magnesium
will slow dissolution of struvite.
Menopause
ANN. CLIN. LAB. SCI. (USA), 1981,
11/4 333-336)
The effect of 100 mg of vitamin
B6 twice a day on plasma and red blood cell (RBC) magnesium
was evaluated in nine premenopausal subjects during the period
of one month. According to reported normal ranges for plasma
and RBC magnesium (1.7 to 2.3 and 4.7 to 7.0, mg per dl, respectively),
three subjects had low plasma magnesium, and all subjects had
low RBC magnesium during the control period. Following vitamin
B6 administration, the mean plasma and RBC magnesium levels
were significantly elevated, with a doubling of RBC levels after
four weeks of therapy. These results support the postulate that
vitamin B6 plays a fundamental role in the active transport
of minerals across cell membranes.
UNITED KINGDOM CLIN. SCI. (ENGLAND),
1980, 58/3 (255-257)
Serum, urinary and erythrocyte
magnesium concentrations were measured in groups of premenopausal,
postmenopausal and oophorectomized women. Serum and urinary
magnesium were both significantly higher in postmenopausal and
oophorectomized women than in the premenopausal group. Oestrogen
therapy reduced both serum and urinary magnesium values in oophorectomized
women to premenopausal concentrations. Erythrocyte magnesium
concentrations were not affected by menstrual status or oestrogen
therapy.
GYNECOL. ENDOCRINOL. (United
Kingdom), 1994, 8/1 (55-58)
Qualitative and quantitative
differences in the dietary habits of postmenopausal women were
studied to assess their influence on bone health and osteoporosis.
A total of 194 postmenopausal women were studied with forearm
DEXA densitometry. 70 were osteoporotic and 124 served as controls.
Women had been menopausal for 5-7 years and had never been treated
with hormone replacement or drug therapy. A 3-day dietary recall
was completed on Sunday, Monday and Tuesday after the examination:
the results were processed by computer and daily calcium, phosphorus
and magnesium intakes were related to bone mineral content (BMC).
Data were compared with Student's t-test and significance was
assessed at p < 0.05. Regression analysis was performed to
correlate BMC and intake levels. The dietary intake of calcium
phosphorus and magnesium was significantly reduced in osteoporotic
women and correlated with BMC. Calcium and magnesium intakes
were lower than the recommended daily allowance even in normal
women. The results suggest that nutritional factors are relevant
to bone health in postmenopausal women, and dietary supplementation
may be indicated for the prophylaxis of osteoporosis. Adequate
nutritional recommendations and supplements should be given
before the menopause, and dietary evaluation should be mandatory
in treating postmenopausal osteoporosis.
Migraine Headache
Headache (UNITED STATES) Mar
1997, 37 (3) p142-52
In recent years, research implicating
biochemical abnormalities in various pathological conditions
has spiraled. Headache is an area in which numerous research
studies have been conducted examining biochemical alterations.
We have noticed several similarities in biochemical changes
reported to occur in migraine and in experimental traumatic
brain injury. The most common symptom in mild head injury or
mild traumatic brain injury is headache which, in many instances,
resembles migraine but has a poorly understood pathophysiology.
Biochemical mechanisms believed to be similar in both conditions
include: increased extracellular potassium and intracellular
sodium, calcium, and chloride; excessive release of excitatory
amino acids; alterations in serotonin; abnormalities in catecholamines
and endogenous opioids; decline in magnesium levels and increase
in intracellular calcium; impaired glucose utilization; abnormalities
in nitric oxide formation and function; and alterations in neuropeptides.
In this paper, these proposed biochemical alterations will be
reviewed and compared. Very similar alterations suggest posttraumatic
headache associated with mild head injury and migraine may share
a common headache pathway. (114 Refs.)
Med Hypotheses (ENGLAND) Dec
1996, 47 (6) p461-6
Although the pathogenesis of
migraine is still poorly understood, various clinical investigations,
as well as consideration of the characteristic activities of
the wide range of drugs known to reduce migraine incidence,
suggest that such phenomena as neuronal hyperexcitation, cortical
spreading depression, vasospasm, platelet activation and sympathetic
hyperactivity often play a part in this syndrome. Increased
tissue levels of taurine, as well as increased extracellular
magnesium, could be expected to dampen neuronal hyperexcitation,
counteract vasospasm, increase tolerance to focal hypoxia and
stabilize platelets; taurine may also lessen sympathetic outflow.
Thus it is reasonable to speculate that supplemental magnesium
taurate will have preventive value in the treatment of migraine.
Fish oil, owing to its platelet-stabilizing and antivasospastic
actions, may also be useful in this regard, as suggested by
a few clinical reports. Although many drugs have value for migraine
prophylaxis, the two nutritional measures suggested here may
have particular merit owing to the versatility of their actions,
their safety and lack of side-effects and their long-term favorable
impact on vascular health. (94 Refs.)
Cephalalgia (NORWAY) Jun 1996,
16 (4) p257-63
In order to evaluate the prophylactic
effect of oral magnesium, 81 patients aged 18-65 years with
migraine according to the International Headache Society (IHS)
criteria (mean attack frequency 3.6 per month) were examined.
After a prospective baseline period of 4 weeks they received
oral 600 mg (24 mmol) magnesium (trimagnesium dicitrate) daily
for 12 weeks or placebo. In weeks 9-12 the attack frequency
was reduced by 41.6% in the magnesium group and by 15.8% in
the placebo group compared to the baseline (p < 0.05). The
number of days with migraine and the drug consumption for symptomatic
treatment per patient also decreased significantly in the magnesium
group. Duration and intensity of the attacks and the drug consumption
per attack also tended to decrease compared to placebo but failed
to be significant. Adverse events were diarrhea (18.6%) and
gastric irritation (4.7%). High-dose oral magnesium appears
to be effective in migraine prophylaxis.
Headache (UNITED STATES) Jun
1996, 36 (6) p357-61
Headache has often been described
in the hyperexcitability syndrome which recognizes an alteration
of calcium and magnesium status in its etiopathogenesis. Moreover,
in migraine patients magnesium has been shown to play an important
role as a regulator of neuronal excitability and, therefore
hypothetically, of headache. The present research involves a
neurophysiological evaluation and magnesium status assessment
of a group of headache patients. Nineteen patients (15 women
and 4 men) with episodic tension-type headache and 30 patients
(27 women and 3 men) with migraine without aura were examined.
An ischemic test was carried out on the right arm with electromyographic
(EMG) recording of motor unit potential activity during the
interictal period. The determination of extracellular (serum
and saliva) and intracellular (red and mononuclear blood cells)
magnesium was also performed. The EMG test was positive in 25
of 30 migraine patients and in 2 of 19 tension-type headache
patients. Between the two patient groups, there were no significant
variations in the concentration of extracellular and white blood
cell magnesium, while the red blood cell concentration of this
mineral in the group of migraineurs was significantly reduced
with respect to that in the group of tension-type headache patients
(P < 0.05). The positive EMG test was significantly associated
with a low concentration of red blood cell magnesium (P <
0.0001). These results confirm previous findings by demonstrating
different etiopathogenic mechanisms as the basis of migraine
and tension-type headache. Migraine seems to be related to an
altered magnesium status, which manifests itself by a neuromuscular
hyperexcitability and a reduced concentration in red blood cells.
Multiple Sclerosis
Acta Neurologica Scandinavica
(Denmark), 1995, 92/1 (109-111)
There are few reports of Mg in
MS and none dealing with Mg content in erythrocytes. Mg concentration
was determined in serum and in erythrocytes with the help of
a BIOTROL Magnesium Calmagite colorimetric method (average sensitivity:
0.194 A per mmol/I) and a Hitachi autoanalyzer in 24 MS patients
(7 men and 17 women, age 29-60; 37 years on average with the
duration of the disease: 3-19; 11 years on average, at clinical
disability stages according to the Kurtzke scale: 1-7; 3.2 on
average, in remission stage. A statistically significant decrease
(p < 0.001) of Mg concentration in erythrocytes and no changes
in plasma of MS patients were found. The results obtained suggest
the presence of changes in membrane of erythrocytes which could
be connected with their shorter life and with affection of their
function.
ACTA NEUROL. SCAND. (Denmark),
1990, 81/3 (197-200)
Magnesium (Mg) concentrations
were studied in the brains of 4 patients with definite multiple
sclerosis (MS) and 5 controls. The magnesium contents were determined
by inductively coupled plasma emission spectrometry in autopsy
samples taken from 26 sites of central nervous system tissues,
and visceral organs such as liver, spleen, kidney, heart and
lung. The average Mg content in the CNS tissues, as well as
visceral organs except for spleen, of MS patients showed a significantly
lower value than that seen in control cases. The most marked
reduction of Mg content was observed in CNS white matter including
demyelinated plaques of MS samples. Whether or not these significantly
lower Mg contents found in CNS and visceral organs of MS patients
may play an essential role in the demyelinating process remain
unclear, requiring further studies on MS pathogenesis from the
point of metal metabolism.
Multiple sclerosis: Decreased
relapse rate through dietary supplementation with calcium, magnesium
and vitamin D
MED. HYPOTHESES (UK), 1986, 21/2
(193-200)
(no abstract)
Magnes Res (ENGLAND) Dec 1992,
5 (4) p295-302
The proposed aetiologies of multiple
sclerosis (MS) have included immunological mechanisms, genetic
factors, virus infection and direct or indirect action of minerals
and/or metals. The processes of these aetiologies have implicated
magnesium. Magnesium and zinc have been shown to be decreased
in central nervous system (CNS) tissues of MS patients, especially
tissues such as white matter where pathological changes have
been observed. The calcium content of white matter has also
been found to be decreased in MS patients. The interactions
of minerals and/or metals such as calcium, magnesium, aluminum
and zinc have also been evaluated in CNS tissues of experimental
animal models. These data suggest that these elements are regulated
by pooling of minerals and/or metals in bones. Biological actions
of magnesium may affect the maintenance and function of nerve
cells as well as the proliferation and synthesis of lymphocytes.
A magnesium deficit may induce dysfunction of nerve cells or
lymphocytes directly and/or indirectly, and thus magnesium depletion
may be implicated in the aetiology of MS. The action of zinc
helps to prevent virus infection, and zinc deficiency in CNS
tissues of MS patients may also be relevant to its aetiology.
Magnesium interacts with other minerals and/or metals such as
calcium, zinc and aluminum in biological systems, affecting
the immune system and influencing the content of these elements
in CNS tissues. Because of these interactions, a magnesium deficit
could also be a risk factor in the aetiology of MS.
IDEGGYOG.SZLE (HUNGARY), 1973,
26/7 (307-312)
A study of the action of magnesium
on the centrocecal scotoma in multiple sclerosis revealed that
the scotomas were transiently reduced by magnesium infusions
or that calcium ionization was modified by alkalinization or
Na EDTA.
Osteoporosis
Osteoporosis International (United
Kingdom), 1996, 6/6 (453-461)
Osteoporosis and magnesium (Mg)
deficiency often occur in malabsorption syndromes such as gluten-sensitive
enteropathy (GSE). Mg deficiency is known to impair parathyroid
hormone (PTH) secretion and action in humans and will result
in osteopenia and increased skeletal fragility in animal models.
We hypothesize that Mg depletion may contribute to the osteoporosis
associated with malabsorption. It was our objective to determine
Mg status and bone mass in GSE patients who were clinically
asymptomatic and on a stable gluten-free diet, as well as their
response to Mg therapy. Twenty-three patients with biopsy-proven
GSE on a gluten-free diet were assessed for Mg deficiency by
determination of the serum Mg, red blood cell (RBC) and lymphocyte
free Mg2+, and total lymphocyte Mg.
Fourteen subjects completed a 3-month treatment period in which
they were given 504-576 mg MgCl2 or Mg lactate daily. Serum
PTH, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and osteocalcin
were measured at baseline and monthly thereafter. Eight patients
who had documented Mg depletion (RBC Mg2+
< 150 microM) underwent bone density measurements of the
lumbar spine and proximal femur, and 5 of these patients were
followed for 2 years on Mg therapy. The mean serum Mg, calcium,
phosphorus and alkaline phosphatase concentrations were in the
normal range. Most serum calcium values fell below mean normal
and the baseline serum PTH was high normal or slightly elevated
in 7 of the 14 subjects who completed the 3-month treatment
period. No correlation with the serum calcium was noted, however.
Mean serum 25-hydroxyvitamin D, 1,25-dihydroxy vitamin D and
osteocalcin concentrations were also normal. Despite only 1
patient having hypomagnesemia, the RBC Mg2+
(153 + or - 6.2 microM; mean plus or minus SEM) and lymphocyte
Mg2+ (182 plus or minus 5.5 microM)
were significantly lower than normal (202 + or - 6.0 microM,
P < 0.001, and 198 + or - 6.8 microM, p < 0.05, respectively).
Bone densitometry revealed that 4 of 8 patients had osteoporosis
of the lumbar spine and 5 of 8 had osteoporosis of the proximal
femur (T-scores less than or equal to -2.5). Mg therapy resulted
in a significant rise in the mean serum PTH concentration from
44.6 + or - 3.6 pg/ml to 55.9 plus or minus 5.6 pg/ml (p <
0.05). In the 5 patients given Mg supplements for 2 years, a
significant increased in bone mineral density was observed in
the femoral neck and total proximal femur. This increase in
bone mineral density correlated positively with a rise in RBC
Mg2+. This study demonstrates that
GSE patients have reduction in intracellular free Mg2+,
despite being clinically asymptomatic on a gluten-free diet.
Bone mass also appears to be reduced. Mg therapy resulted in
a rise in PTH, suggesting that the intracellular Mg deficit
was impairing PTH secretion in these patients. The increase
in bone density in response to Mg therapy suggests that Mg depletion
may be one factor contributing to osteoporosis in GSE.
Nutrition Reviews (USA), 1995,
53/3 (71-74)
Among other things, magnesium
regulates active calcium transport. As a result, there has been
a growing interest in the role of magnesium (Mg) in bone metabolism.
A group of menopausal women were given magnesium hydroxide to
assess the effects of magnesium on bone density. At the end
of the 2-year study, magnesium therapy appears to have prevented
fractures and resulted in a significant increase in bone density.
Premenstrual Syndrome
ACTA OBSTET. GYNECOL. SCAND.
(Denmark), 1994, 73/6 (452-455)
We measured plasma Cu, Zn and
Mg levels in 40 women suffering from premenstrual tension syndrome
(PMTS) and in 20 control subjects by atomic absorption spectrophotometer.
Mean plasma Cu, Zn and Mg levels, the Zn/Cu ratio were 80.2
plus or minus 6.00 microg/dl, 112.6 plus or minus 8.35 microg/dl,
0.70 plus or minus 0.18 mmol/l, and 1.40 plus or minus 0.10
in the PMTS group; and 77.0 plus or minus 4.50 microg/dl, 117.4
plus or minus 9.50 microg/dl, 0.87 plus or minus 0.10 mmol/l,
and 1.51 plus or minus 0.05 in the control group respectively.
The mean Mg level and the Zn/Cu ratio were significantly lower
in PMTS patients than in the control group. Plasma Mg and Zn
levels were diminished significantly during the luteal phase
compared to the follicular phase in PMTS group. Mg deficiency
may play a role in the etiology of PMTS.
OBSTET. GYNECOL. (USA), 1991,
78/2 (177-181)
Reduced magnesium (Mg) levels
have been reported in women affected by premenstrual syndrome
(PMS). To evaluate the effects of an oral Mg preparation on
premenstrual symptoms, we studied, by a double-blind, randomized
design, 32 women (24-39 years old) with PMS confirmed by the
