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.
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 Moos Menstrual Distress Questionnaire. After 2
months of baseline recording, the subjects were randomly assigned to placebo or Mg for two
cycles. In the next two cycles, both groups received Mg. Magnesium pyrrolidone carboxylic
acid (360 mg Mg) or placebo was administered three times a day, from the 15th day of the
menstrual cycle to the onset of menstrual flow. Blood samples for Mg measurement were
drawn premenstrually, during the baseline period, and in the second and fourth months of
treatment. The Menstrual Distress Questionnaire score of the cluster 'pain' was
significantly reduced during the second month in both groups, whereas Mg treatment
significantly affected both the total Menstrual Distress Questionnaire score and the
cluster 'negative affect'. In the second month, the women assigned to treatment showed a
significant increase in Mg in lymphocytes and polymorphonuclear cells, whereas no changes
were observed in plasma and erythrocytes. These data indicate that Mg supplementation
could represent an effective treatment of premenstrual symptoms related to mood changes.
ANN. CLIN. BIOCHEM. (UK), 1986, 23/6 (667-670)
Plasma and erythrocyte magnesium were measured in 105
patients with premenstrual syndrome (PMS) using a simple atomic absorption spectroscopy
method. The erythrocyte magnesium concentration for the patients with PMS was
significantly lower than that of a normal population. The plasma magnesium did not show
this difference. The significance of this apparent cellular deficiency of magnesium is
discussed.
Rheumatoid arthritis
Journal of Rheumatology (Canada), 1996, 23/6 (990-994)
Objective. To determine nutrient intake of patients with
active rheumatoid arthritis and compare it with the typical American diet (TAD) and the
recommended dietary allowance (RDA). Methods. 41 patients with active RA recorded a
detailed dietary history. Information collected was analyzed for nutrient intake of
energy, fats, protein, carbohydrate, vitamins and minerals, which were then statistically
compared with the TAD and the RDA. Results. Both men and women ingested significantly less
energy from carbohydrates (women 47.4% (6.4) vs 55% RDA, p = 0.0001; men = 48.9% (7.4), p
= 0.025) and more energy from fat (women = 36.8% (4.5) vs 30% RDA. p = 0.001 and men =
35.2% (5.9) p = 0.02). Women ingested significantly more saturated and mono-unsaturated
fat than the RDA (p = 0.02 and p = 0.04 respectively) while men ingested significantly
less polyunsaturated fat (PUFA)(p = 0.0001). Both groups took in less fiber (p = 0.0001).
Deficient dietary intake of pyridoxine was observed vs the RDA for both sexes (men and
women p = 0.0001). Deficient folate intake was seen vs the TAD for men (p = 0.02) with a
deficient trend in women (p = 0.06). Zinc and magnesium intake was deficient vs the RDA in
both sexes (p values less than or equal to 0.001) and copper was deficient vs the TAD in
both sexes (p = 0.004 women and p = 0.02 men). Conclusion. Patients with RA ingest too
much total fat and too little PUFA and fiber. Their diets are deficient in pyridoxine,
zinc and magnesium vs the RDA and copper and folate vs the TAD. These observations, also
documented in previous studies, suggest that routine dietary supplementation with
multivitamins and trace elements is appropriate in this population.
Trace Elements and Electrolytes (Germany), 1996, 13/2
(85-87)
Plasma, intraleukocytic and intraerythrocytic zinc, copper,
and magnesium levels of patients with rheumatoid arthritis who were and were not receiving
tenoxicam have been determined. The results of the patients who were not receiving
tenoxicam are as follows: plasma levels (micromol/l): zinc 15.4 plus or minus 0.41
(arithmetic mean + standard error of the mean), copper 21.2 plus or minus 0.82, magnesium
1,120 plus or minus 15.8. Intraleukocytic levels (ng/106 cells) zinc 17.5 plus or minus
2.64, copper 0.451 plus or minus 0.064, magnesium 60.0 plus or minus 5.68.
Intraerythrocytic levels (microg/1010 cells): zinc 5.20 plus or minus 0.61, copper 2.64
plus or minus 0.44, magnesium 66.1 plus or minus 4.87. There was no significant difference
between all 3 element levels of patients who were or were not receiving tenoxicam. Plasma,
leukocyte, and erythrocyte zinc levels of both groups of patients were lower (p <
0.001), copper levels were higher (p < 0.001) than those of healthy subjects. Plasma
and leukocyte magnesium levels of both groups of patients and only erythrocyte magnesium
levels of patients receiving tenoxicam were higher (p < 0.01) than those of healthy
control group.
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