ArticlePDF Available

Magnesium-L-aspartate-HCl and magnesium-oxide: bioavailability in healthy volunteers

DOI:10.1007/BF00265863
Authors:
Bernd Mühlbauer at Universität Bremen
Bernd Mühlbauer
M Schwenk
M Schwenk
M Schwenk
  • This person is not on ResearchGate, or hasn't claimed this research yet.
W M Coram
W M Coram
W M Coram
  • This person is not on ResearchGate, or hasn't claimed this research yet.
Karl-Heinz Antonin at Praxis
Karl-Heinz Antonin
Show all 7 authorsHide
Download full-text PDF
Read full-text
Download citation

Abstract

Magnesium deficiency can occur in several diseases. such as malabsorption syndromes, diabetes mellitus and renal disorders. It can be treated with oral magnesium compounds, of which several preparations are currently available: various complex salts, and the oxide or hydroxide of magnesium [1]. In the present study, two formulations of magnesium-L-asparate HCI (Magnesiocard® tablets and Magnesiocard® granules, Verla-Phann, FRG) were compared with magnesium-oxide (Magnetrans® forte capsules, Fresenius, FRG) with respect to bioavailability, tolerability, and stool frequency. The three magnesium preparations were each administered in an open manner to 3 groups of 8 healthy volunteers according to a parallel group design. The groups of 4 males and 4 females each were comparable with regard to age, height and body weight. After a control and a placebo period of one week, 60 mEq/d and 90 mEq/d magnesium were administered for 7 days each. No special diet was given. Cumulative urinary magnesium excretion was used to assess magnesium absorption [2. 3]. Plasma and urine concentrations of magnesium. potassium and calcium were measured by atome emission spectromtryusing a Spectraspan SR (ARL). Urine pH was assessed with indicator strips (Spezialindikator pH 4.0-7.0. Merck. Darmstadt ). Stool frequency was evaluated by the volunteers, recording the time and number of stools. Mouth to caecum transit time was estimated using salazosulfapyridine (SASP) as the test compound [4], measuring SP in saliva by a specific and selective HPLC method [5]. Means and SDs of the parameters were calculated and tested by analysis of variance (ANOVA, randomized factorial design) for differences. 95% confidence intervals were calculated for cumulative urinary magnesium excretion. For statistical analysis of stool frequency, the one criterion variance analysis of Kruskal and Wallis was applied [6]. During the higher magnesium dosage, stool frequency was increased 1.8-fold by magnesium-oxide, 3.2-fold by granules and 2.0-fold by tablets of magnesium-L-aspartate-HCI. The differences between the treatment groups did not reach statistical significance. Mean mouth-caecum transit time of about 4 h was not affected by magnesium treatment, suggesting that the magnesium preparations exerted their laxative effect mainly in the colon. Minor adverse effects were reported in each group, such as flatulence. diarrhoea, and gastric discomfort. There were complaints of an unpleasant taste of the granule formulation, which may influence patients compliance. Urine pH was decreased ( - 0.5) during magnesiumL-aspart ate-HCl and increased ( + 0.5) during magnesium-oxide (P < 0.01) administration, indicating a slight disturbance of the acid/base equilibrium. This aspect may be of clinical importance, particularly in elderly patients with multiple diseases. Calcium and potassium levels in plasma and urine were not altered by magnesium treatment. Plasma magnesium, remained unchanged too. The mean cumulative urinary magensium excretion was similar during the placebo and control periods, ranging from 77.5 to 93 .7 mEq/week. There was a significant increase during magnesium administra tion,more marked during the Mg-L-asparta te-HCl phase (P < 0.0001). The maximum value of 187.4 mEq/week was reached during treatment with magnesium-L-asparateHCI granules 90 mEq/d. The differences between the three treatment groups indicated better absorption of magnesium-L-asparate-HCI than of magnesium-oxide. One possible explanation might be the poor solubility of magnesium-oxide, which in water is 8.6 mg/di [7]. In conclusion, all three formulations of magnesium given in the trial were well tolerated, but they increased the number of stools. Magnesium-oxide showed significantly lower absorption than magnesium L-asparate-HCI. As there were complaints of an unpleasant taste of the resuspended granules, tablets of magnesium-L-aspartateHCI appear to be the first choice for magnesium substitution among the formulations investigated. References 1. Mudge GH, Weiner IM (1990) Agents affecting volume and composition of body fluids. In: Gilman AG, Ra ll TW, Nies AS, Taylor P (eds) The pharmacological basis of therapeutics 8th ed ., Pergamon, New York, pp 682-707 2. Drenick EJ , Hunt IF, Swcndscid ME ( 1969) Magnesium depletion during prolonged fasting of obese males. J Cl in Endocrinol Metab 29: 1341 - 1348 3. Lim P. Jacob E (1972) Magnesium status of alcoholic patients. Metabolism 2 1: 1045- 1051 4. Kennedy M, Chinwah P, Wade DN (1979) A pharmacological method of measuring mouth to caecum transit time in man. Br J Cl in Pharmacol 8: 372- 373 5. Owerbach J . Johnson NF, Bates TR, Pi eniaszek HJ , Jusko WJ ( 1987) High performance liquid chromatographic assay of sulfapyridinc and acetylsulfapyridine in biological fluids. J Pharm Sci 67:250-253 6. Kruskal WH. Wallis WA (I952) Use of ranks in one-criterion variance analysis. J Am Stat Assoc 47: 583-621 7. Weast RC (1975) Handbook of chemistry and physics, 55th ed. Cleveland. CRC Press, B-106
Content uploaded by Peter Bieck
Author content
All content in this area was uploaded by Peter Bieck on Oct 09, 2015
Content may be subject to copyright.
E
ur
J Cl
in
Pharm acol ( 1
99
1) 40: 437-438
003169709100108G
Eu
ropean Journ
al
of
CSIJO
@
DcsGJO
LJ1Tu@~D~~
©S
pringe
r-
Ve
rl
ag 1991
Magnesium-L-aspartate-HCI and magnesium-oxide:
bioavailability in healthy volunteers
B.
Miihlbauer1,
M.
Schwenk1,
W.
M.
Coram2, K.
H.
Antonin 1,
P.
Etienne2, P.R. Bieck 1,
and
F.
L.
Douglas2
1
Hum
an Pharmacology Institute. Ci
ba-Ge
igy G
mbH
. T
ii
bingen. FRG
' Pharmaceuticals Division. Ciba-
Ge
i
gy
Co
r
po
ra
ti
o
n.
S
ummit
J. USA
Received: January 28. 1990/Acccpt cd
in
revised form:
Octo
ber 19. 1990
Ke
y
words:
Magnesium de
fici
ency,
ora
l repl acement ther-
apy. bi
oava
il
abilit
y,
adverse e
ff
ects
Magnesium de
fi
ciency can occ
ur
in several
di
seases. such
as malabs
orpti
on
sy
ndrom
es, di abetes mellitus
and
renal
di
so
rder
s.
It
can be
tr
ea
ted with oral magnesium com-
po
und
s,
of
which several
pr
e
parati
ons are
curr
ently
ava
il-
able : va rious
co
mplex sa
lt
s, and the oxide or hyd rox
id
e of
magnesium [1 ]. In the
pr
esent s
tud
y,
two formulations of
magnesium-L-asp
ara
te HC I (MagnesiocardR ta
bl
ets and
Magnesioca
rdR
gra
nules, Ve
rl
a
-Phann
,
FR
G)
were com-
pared with
ma
gnesium-oxide (Magnetran
sR
fo
rte cap-
sules,
Fr
esenius,
FRG
) with respect to
bi
oava
ilability,
tol
era
bility, a
nd
st
oo
l
fr
e
qu
enc
y.
Th
e
thr
ee
magnesium
pr
ep
ara
tions were
ea
ch adminis-
tered in an open manner to 3
gro
ups
of
8 h
ea
lthy volun-
t
ee
rs according to a para
ll
el g
roup
desig
n.
Th
e gro
up
s
of
4 males and 4
fe
males
ea
ch were co
mparabl
e with regard
to age, heig
ht
and body weight. A
ft
er
a control and a
pl
acebo period of one
wee
k, 60
mEq
/d and 90
mEq
/d
magnesium were administered for 7 days
eac
h.
No
sp
ec
ial
di
et was given. Cumula
ti
ve urinary magnesium excretio n
was used to assess magnesium absorptio n [2. 3]. Plasma
and urine concentrations of magnesium. potassium and
calcium were measured by atome emissio n spectrome
tr
y
us
in
g a Spectraspan
SR
(
ARL
).
Urine
pH
was assessed
wi
th indicator strips (Sp
ez
ia
lindikator
pH
4.
0
-7.
0. Merck.
Darm
stadt). St
oo
l
fr
e
qu
ency was
eva
luated by the volun-
t
ee
rs, recording
th
e time and
numb
er of st
oo
ls. Mouth to
cae
cum
transit time was estimated us
in
g salazos
ul
fa
py-
ridine (
SASP
) as the test co
mp
o
und
[4]. measuring SP
in
sa
li
va by a specific
and
selective
HPL
C me
th
od [5
].
M
ea
ns and
SD
s of
th
e pa
ram
eters were calc
ul
ated and
tested by anal
ys
is of variance (AN
OY
A. randomized fac-
torial design) for diffe rences. 95% confidence intervals
were ca lculated
fo
r cumula
ti
ve urinary magnesium ex
cr
e-
tion. For statist
ic
al analysis of st
oo
l
fr
e
qu
en
cy
. the one
crite
ri
on variance anal
ys
is of Kruskal and Wallis was ap-
plied [6
].
Durin
g the
hi
gher magnesium dosage, st
oo
l
fr
e
qu
e
nc
y
was
in
cr
eased
1.
8-
fo
ld by magnesium-oxide, 3.2-
fo
ld by
gra
nules and 2.0-
fo
ld
by tablets of
ma
gnesium-L-aspa
r-
tate-HC
I.
Th
e differences between the
tr
ea
tment
gro
ups
did not r
eac
h sta
ti
stical significance. M
ea
n mouth-c
ae
cum
trans
it
time
of
ab
out 4 h was not affected by magnesium
tr
ea
tment, suggesting
th
at
th
e magnesium
pr
eparations
exerted
th
eir laxative e
ff
ect mainly in
th
e colo
n.
Minor
ad-
verse e
ff
ec
ts were reported in
ea
ch
gro
up
, such as
fl
a-
tule nce. diarrh
oea
, and gastric discomfor
t.
Th
ere were
complaints
of
an unpl
easa
nt taste of the granule
fo
rmula-
ti
on. which may influence patients compliance.
Urine
pH
was de
cr
eased ( -
0.
5) during
ma
gnesium-
L-aspartate
-H
Cl and
in
cr
ease
d ( + 0.5) during magne-
sium-oxide (P < 0.01) administration. indicating a s
li
g
ht
dis
turb
ance of the
ac
id
/base equilibrium.
Th
is
aspect may
be of clinical impor
ta
nce, pa rticula
rl
y in e
ld
erly patients
with multiple diseases. Calcium and po tassium l
eve
ls in
plasma and urine were not a
lt
ered by magnesium
tr
eat-
ment.
Pl
asma magnesium, rema
in
ed
unchan
ged too.
Th
e m
ea
n cumula
ti
ve urinary magensium ex
cr
etion
(Tab. 1) was similar during the placebo and control peri-
od
s.
rang
in
g
fr
om 77.5 to
93
.7
mEq/w
ee
k.
Th
ere
was a
significant increase during magnesium administra
ti
on,
more marked during
th
e Mg-L-asp
ar
tate-HCl
pha
se
(P < 0.0001).
Th
e maximum value
of
187.4 mEq/week was
Table 1. Total 7 day cumula
ti
ve urin ary magnesium excre
ti
on
(mEq/
24
h ··· 7d) during administra
ti
on
of
Mg-L-aspartatc-H
CI
(gra-
nules and tablets) and Mg-oxi
de
caps
ul
es in comparison with cont ro l
(no treatment) and placebo. Mean values (95% confidence inte
r-
vals) in 8 volunt
eers
are give
Pe
ri
ods days 0- 7 days
8-
14 days 1
5-2
1 days 22-28
Treatm ent /
dose
control pl
acebo
60 mEq/d 90 mEq/d
Mg-L-aspartatc- 78 84 146 1
81
HC I ta
bl
ets
(54-
101) (59- l I 0) (108- 184) ( 137-225)
Mg-L-aspartatc- 91 81 156 187
H C
l-
granules (61- 120)
(56-
106) (
11
3- 199) ( 15 1- 224)
Mg-ox ide
94
90 133 137
caps
ul
es
(76-
111
)
(74-
105) ( I I 1
-155)
(
11
5- 159)
438
reached
during
treatment
with magnesium-L-asparate-
HCI granules 90
mEq
/d.
Th
e differences
betwe
en
the
thr
ee
treatm
ent
groups
indicated
better
absorption
of
magnesium-L-asparate-HCI
than
of
magnesium-oxide.
On
e possible ex
planation
might
be
the
poor
solubility
of
magnesium-oxide, which
in
water
is 8.6 mg/di
[7]
.
In conclusion, all
three
formulations
of
magnesium
given
in
the trial
were
well
tolerated
,
but
they increased
the
number
of
stools. Magnesium-oxide
showed
signifi-
cantly lower
absorption
than
magnesium L-asparate-HCI.
As
there
were complaints
of
an
unpleasant
taste
of
the
re-
suspended
granules, tablets
of
magnesium-L-aspartate-
HCI
appear
to
be the first choice for
magne
sium substitu-
tion
among
the
formulations investigated.
References
1.
Mudge
GH
, Weine r IM (1990)
Agents
affecting volume
and
com-
position
of
body fluids. In: Gilman
AG
, Ra
ll
TW
, Nies AS, Taylor
P (eds)
The
pharmacological basis
of
th
erape
utics 8th ed
..
Perga-
mon, New York , pp 682-707
Announcements
International
Boerhaal
'e Course
on
Drug-Drug and Drug-Food
Interactions. Mechanisms, Study Design and Clinical Significance
2-3
May.
1991
Leid
en
,
The
Netherlands
For
f1mher
i11f
o
r111ari
o11
please
co
11w
c1:
Course
Secretariat
Bo
er
haave
Committee
P.
0.
B
ox
2084
NL-2301 CB Leiden
The
Netherlands
Tel.: (31) 7127 52
97
Fax: (3
1)
71275262
TroisiCme Symposium International de Neuropharmacologie
Clinique
"Third
International Symposium
on
Clinical
Neuropharmacology"
13
-
15Juin
,
1991
Marseille,
France
Forf1mher
i11f
o
r111ari
o
11
please co
11w
c1:
Secretariat
Dr
.
0.
Blin
Cliniquc des Maladies du Systeme Nerve
ux
et
de
l'Appareil
Locomoteur
(Pr
G. Serratrice)
CHU
la
Timone
F-13385 Marseille cedex 5
France
The
7th International Conference on Pharmacoepidemiology
26-29 August,
1991
Basel, Switzerland
(E
urop
ean World
Trade
and
Co
nvention
Center)
For
f11r1her
i11f
or
111a1i
o
11
please co
11w
c
1:
Dr. Stanley A.
Ed
lavitch
Conference
Chair
ISPE Office
Univers
it
y
of
Minnesota
B.
Muhlbauer
et al.: Bioavail
ab
ility
of
magnesium
2.
Drenick EJ,
Hunt
IF
, Swcndscid
ME
(
196
9) Magnesium depletion
during
prolonged
fasting
of
obese
males. J Cl
in
Endocrinol
Metab
29:
1341
-1348
3. Lim
P.
Jacob
E (1972) Magnesium status
of
a
lc
oholic patients. Me-
t
abo
lism 2 1: 1045-
1051
4.
Kennedy M, Chinwah P, Wade DN (1979) A pharmacological
me
thod
of
measuring
mouth
to caecum tran
si
t time
in
man.
Br
J
Cl
in
Pharmacol
8:
372-373
5.
Owerbach
J.
Johnson
NF,
Bates
TR
,
Pi
eniaszek HJ,
Jusko
WJ
( 1987) High
performance
liquid
chromatographic
assay
of
sulfa-
pyridinc and acetylsulfapyridine in biological fluids. J Pharm
Sci
67:250-253
6.
Kruska l
WH.
Wallis WA (I 952) Use
of
ranks
in
one-criterion vari-
ance anal
ys
i
s.
J
Am
Stat Assoc 47: 583-621
7.
Weast RC (1975)
Handb
oo
k of chemistry and physics, 55th ed.
Cleveland. CR C Press, B-106
B.
MOhlbaucr, M. D.
Human
Pharmacolo
gy
Institute
(HPI)
Ciba
-G
eigy
GmbH
Waldhornlestral3c
22
W-7400 TUbingen,
FRG
Co
ll
ege
of
Pharmacy
HSUF7-15
8
308
Harvard
Street
S.
E.
Minneapolis, MN 55455,
USA
Tel.: (612) 624-4426/5931
Fax: (6 12) 624-2974
1st World Congress
of
Cellular and Molecular Biology
1- 7
September
, 1991
Paris-Versailles (Palais
des
Congres)
For
jimher
i11f
o
n11a1ion
please comae/:
Mrs. Leila Orbecchi
Dir
e
ktor
C.E.R.T.
63
, Avenue
Parmentier
F-7501 l Paris, France
Tel.:(1)48070700
Fax: (1) 48072211
Second Jerusalem Conference
on
Pharniaceutical Sciences
and Clinical Pharmacology
24-29 May, 1992
Jerusa lem , Israel
Forf11r1her
i11f
o
r111a1io11
please comae!:
Pro
f.
Meir Bialer
P.
0.
Box 50006
Tel Aviv 61500
Israel
... There is a corollary between the solubility of magnesium compounds and their subsequent bioavailability-the more soluble the supplement, typically, the greater the bioavailability [34][35][36]. As such, although magnesium oxide is commonly used as a magnesium supplement for its~60% magnesium composition, it lacks substantial water solubility and exhibits lower bioavailability than other organic magnesium salts [34,36]. ...
... There is a corollary between the solubility of magnesium compounds and their subsequent bioavailability-the more soluble the supplement, typically, the greater the bioavailability [34][35][36]. As such, although magnesium oxide is commonly used as a magnesium supplement for its~60% magnesium composition, it lacks substantial water solubility and exhibits lower bioavailability than other organic magnesium salts [34,36]. While the chloride and sulfate magnesium salts exhibit substantial water solubility, they rapidly dissociate and leave available reactive sites on the Mg 2+ site, making it more susceptible to precipitating from bioagents, such as phytates, and hydration-thus resulting in laxation [3,[37][38][39]. ...
... While there are many physiological factors that have been shown to contribute to magnesium bioavailability during supplementation, such as age [39], dose load [60], and frequency [61,62], there are also chemical factors that impact magnesium bioavailability, such as chemical composition and solubility [34][35][36]63]. The solubility of MgG 3 was found to be approximately 169 ± 12.5 g/100 mL H 2 O, which is approximately three times more soluble than the next closest magnesium supplement (MgCl 2 at 54 g/100 mL-see Table 1) and, as such, shows great promise for cellular uptake, as it is believed this increase in solubility will aid in bioavailability. ...
Synthesis and Chemical and Biological Evaluation of a Glycine Tripeptide Chelate of Magnesium
Article
Full-text available
Magnesium (Mg2+) plays a crucial role in over 80% of all metabolic functions. It is becoming increasingly apparent that magnesium deficiency (hypomagnesemia) may play an important role in chronic disease. To counteract magnesium deficiency, there is an unmet clinical need to develop new fully characterized, highly bioavailable, and substantially water-soluble magnesium supplements. To this end, triglycine (HG3), a tripeptide of the amino acid glycine, was chosen as a chelating ligand for magnesium, given its natural occurrence and water solubility, and entropically-driven metal binding. Herein, we discuss the synthesis, chemical and physical characterization, and cellular uptake of a magnesium triglycine chelate (MgG3), an octahedral complex with extraordinary water solubility and improved cellular uptake in CaCo-2 cells than select commonly used magnesium supplements.
... Other magnesium salts have been studied in a limited number of studies in humans conducted in the early 1990s, with mixed results. In some studies, there was no difference between organic and inorganic magnesium salts [76][77][78][79]; others demonstrated slightly higher bioavailability of organic magnesium salts under standardized conditions [18,34,[80][81][82][83]. Magnesium pidolate is an organic salt and organic salts have been found to be consistently more bioavailable that inorganic salts in many human studies. ...
... In some studies, there was no difference between organic and inorganic magnesium salts [76][77][78][79]; others demonstrated slightly higher bioavailability of organic magnesium salts under standardized conditions [18,34,[80][81][82][83]. Magnesium pidolate is an organic salt and organic salts have been found to be consistently more bioavailable that inorganic salts in many human studies. Despite the lack of studies specifically analyzing magnesium pidolate bioavailability, it could be postulated that magnesium pidolate availability is, in part, due to its organic properties [18,34,[80][81][82][83]. ...
Headaches and Magnesium: Mechanisms, Bioavailability, Therapeutic Efficacy and Potential Advantage of Magnesium Pidolate
Article
Full-text available
  • Aug 2020
Magnesium deficiency may occur for several reasons, such as inadequate intake or increased gastrointestinal or renal loss. A large body of literature suggests a relationship between magnesium deficiency and mild and moderate tension-type headaches and migraines. A number of double-blind randomized placebo-controlled trials have shown that magnesium is efficacious in relieving headaches and have led to the recommendation of oral magnesium for headache relief in several national and international guidelines. Among several magnesium salts available to treat magnesium deficiency, magnesium pidolate may have high bioavailability and good penetration at the intracellular level. Here, we discuss the cellular and molecular effects of magnesium deficiency in the brain and the clinical evidence supporting the use of magnesium for the treatment of headaches and migraines.
... The bioavailability of elementary magnesium may vary in each of these individual compounds and is still the subject of experimental work and clinical studies. Clinical trials have investigated multiple magnesium compounds in order to determine the most suitable for magnesium supplementation by comparison their respective bioavailability (Kappeler et al. 2017, Bøhmer et al. 1990, Gegenheimer et al. 1994, Lindberg et al. 1990, Firoz et al. 2001, Muehlbauer et al. 1991, Walker et al. 2003. Clinical trials have generally tried to analyse magnesium bioavailability and specifically the compare organic and inorganic magnesium salt sources, (Ranade et al. 2001, Wolf et al. 2003, Kappeler et al. 2017 focusing primarily on evaluation of urinary excretion or serum levels. ...
A New Caco-2 Cell Model of in Vitro Intestinal Barrier: Application for the Evaluation of Magnesium Salts Absorption
Article
Experimental data concerning the bioavailability of the different Mg-salts in human organism is inconsistent. Mg-absorption reported by clinical studies largely varies depending on the method used for evaluation. The aim of this study was to evaluate the bioavailability and accessibility of magnesium bound in different Mg-salt compounds, using an in vitro model of intestinal cell barrier. The study included a variety of inorganic (oxide, sulphate, chloride, carbonate) and organic salts (lactate, citrate, pidolate). Caco-2 cells were cultivated in a complete culture medium with different magnesium salts treatments in ascending concentrations. The viability and quantity of cells was analysed by FACS. Mg-absorption was analysed by a direct colorimetric assay, measured by spectrometry. T-test identified a significant decrease in cell count treatment with mg-lactate compared with citrate. Mg-pidolate showed a significantly higher cell viability compared with Mg-citrate, Mg-lactate and Mg-chloride. Even though the difference was not significant, we showed that an increase in Mg2+ salt concentration progressively decreased the cell count and the viability and the effect was universal for all the used Mg-salt treatments. Mg-citrate, chloride, and sulphate showed a significantly lower absorption compared to Mg-carbonate, pidolate and oxide. Our in vitro monolayer model of human intestinal transport showed that viability and quantity of cell decreased with increasing Mg-concentration. We admit that our experiment model may have some limitations in accurately describing an in vivo Mg2+ absorption. Moreover, it is also necessary to assess the relevance of our data in vivo and especially in clinical practice.
... However, magnesium oxide is still used due to a significant share in the percentage of magnesium ion in this preparation (60%). Organic magnesium compounds are characterized by greater solubility in water compared to inorganic compounds, which causes much better absorption in the small intestine, reaching the value of 90% [67][68][69]. The highest absorption of magnesium in an organic form was found for its chelate with citrate after oral administration in healthy people. ...
Magnesium as an Important Factor in the Pathogenesis and Treatment of Migraine—From Theory to Practice
Article
Full-text available
  • Mar 2022
So far, no coherent and convincing theory has been developed to fully explain the pathogenesis of migraine, although many researchers and experts emphasize its association with spreading cortical depression, oxidative stress, vascular changes, nervous excitement, neurotransmitter release, and electrolyte disturbances. The contribution of magnesium deficiency to the induction of cortical depression or abnormal glutamatergic neurotransmission is a likely mechanism of the magnesium–migraine relationship. Hence, there is interest in various methods of assessing magnesium ion deficiency and attempts to study the relationship of its intra- and extracellular levels with the induction of migraine attacks. At the same time, many clinicians believe that magnesium supplementation in the right dose and form can be a treatment to prevent migraine attacks, especially in those patients who have identified contraindications to standard medications or their different preferences. However, there are no reliable publications confirming the role of magnesium deficiency in the diet as a factor causing migraine attacks. It also seems interesting to deepen the research on the administration of high doses of magnesium intravenously during migraine attacks. The aim of the study was to discuss the probable mechanisms of correlation of magnesium deficiency with migraine, as well as to present the current clinical proposals for the use of various magnesium preparations in complementary or substitute pharmacotherapy of migraine. The summary of the results of research and clinical observations to date gives hope of finding a trigger for migraine attacks (especially migraine with aura), which may turn out to be easy to diagnose and eliminate with pharmacological and dietary supplementation.
... The bioavailability of elementary magnesium may vary in each of these individual compounds and is still the subject of experimental work and clinical studies. Clinical trials have investigated multiple magnesium compounds in order to determine the most suitable for magnesium supplementation by comparison their respective bioavailability (Kappeler et al. 2017, Bøhmer et al. 1990, Gegenheimer et al. 1994, Lindberg et al. 1990, Firoz et al. 2001, Muehlbauer et al. 1991, Walker et al. 2003. Clinical trials have generally tried to analyse magnesium bioavailability and specifically the compare organic and inorganic magnesium salt sources, (Ranade et al. 2001, Wolf et al. 2003, Kappeler et al. 2017 focusing primarily on evaluation of urinary excretion or serum levels. ...
A New Caco-2 Cell Model of in Vitro Intestinal Barrier: Application for the Evaluation of Magnesium Salts Absorption
Article
  • Nov 2021
Experimental data concerning the bioavailability of the different Mg-salts in human organism is inconsistent. Mg-absorption reported by clinical studies largely varies depending on the method used for evaluation. The aim of this study was to evaluate the bioavailability and accessibility of magnesium bound in different Mg-salt compounds, using an in vitro model of intestinal cell barrier. The study included a variety of inorganic (oxide, sulphate, chloride, carbonate) and organic salts (lactate, citrate, pidolate). Caco-2 cells were cultivated in a complete culture medium with different magnesium salts treatments in ascending concentrations. The viability and quantity of cells was analysed by FACS. Mg-absorption was analysed by a direct colorimetric assay, measured by spectrometry. T-test identified a significant decrease in cell count treatment with mg-lactate compared with citrate. Mg-pidolate showed a significantly higher cell viability compared with Mg-citrate, Mg-lactate and Mg-chloride. Even though the difference was not significant, we showed that an increase in Mg2+ salt concentration progressively decreased the cell count and the viability and the effect was universal for all the used Mg-salt treatments. Mg-citrate, chloride, and sulphate showed a significantly lower absorption compared to Mg-carbonate, pidolate and oxide. Our in vitro monolayer model of human intestinal transport showed that viability and quantity of cell decreased with increasing Mg-concentration. We admit that our experiment model may have some limitations in accurately describing an in vivo Mg2+ absorption. Moreover, it is also necessary to assess the relevance of our data in vivo and especially in clinical practice.
... The neuroprotective effects of Mg (through NMDA receptor blockage and inhibition of glutamate release) are also reported [31]. Organic Mg (Magnesium picolinate; MgPic) is absorbed more completely and is more bioavailable than inorganic Mg (Magnesium oxide (MgO) [32,33]. To our knowledge, no studies on the comparative effects of MgPic and MgO on retinal functions of HFD rats are available in the literature. ...
Different Sources of Dietary Magnesium Supplementation Reduces Oxidative Stress by Regulation Nrf2 and NF-κB Signaling Pathways in High-Fat Diet Rats
Article
Full-text available
Magnesium (Mg) is an essential mineral required for many physiological processes, including ionic balances in ocular tissues. We compared the effects of different Mg-chelates (Mg oxide, MgO vs. Mg picolinate, MgPic) on retinal function in a high-fat diet (HFD) rats. Forty-two rats were divided into six groups and treated orally for 8 weeks as follows: Control, MgO, MgPic, HFD, HFD + MgO, and HFD + MgPic. Mg was administered at 500 mg of elemental Mg/kg of diet. HFD intake increased the levels of retinal MDA and NF-κB, INOS, ICAM, and VEGF but downregulated Nrf2. However, in rats supplemented with MgO and MgPic, the retinal MDA level was decreased, compared with the control and HFD rats. Activities of antioxidant enzymes (SOD, CAT, and GPx) were increased in HFD animals given Mg-chelates (p < 0.001), MgPic being the most effective. Mg supplementation significantly decreased the expression levels of NF-κB, INOS, ICAM, and VEGF in HFD rats while increasing the level of Nrf2 (p < 0.001). Mg supplementation significantly decreased the levels of NF-κB, INOS, ICAM, and VEGF and increased Nrf2 level in HFD rats (p < 0.001), with stronger effects seen from MgPic. Mg attenuated retinal oxidative stress and neuronal inflammation and could be considered as an effective treatment for ocular diseases.
... Furthermore, studies in cats and rats have shown that magnesium-aspartate hydrochloride is significantly better absorbed from the gastrointestinal tract than magnesium sulfate, chloride or aspartate (Classen et al. 1973). In addition, magnesium-aspartate hydrochloride has a better oral bioavailability than magnesium oxide in humans (Mühlbauer et al. 1991). Comparable examinations in horses have not been carried out so far. ...
Relationship between intracellular free magnesium concentration and the degree of insulin resistance in horses with equine metabolic syndrome
Article
... There are many physical factors that were shown to impact magnesium bioavailability, such as dose load/frequency [68][69][70] and age [71]. There are also many chemical factors, most significantly solubility [67,[72][73][74]. The bioavailability of Mg 2+ within the GI exhibits correlative behavior relative to the water solubility of the complex. ...
The Coordination Chemistry of Bio-Relevant Ligands and Their Magnesium Complexes
Article
Full-text available
The coordination chemistry of magnesium (Mg2+) was extensively explored. More recently; magnesium; which plays a role in over 80% of metabolic functions and governs over 350 enzymatic processes; is becoming increasingly linked to chronic disease-predominantly due to magnesium deficiency (hypomagnesemia). Supplemental dietary magnesium utilizing biorelevant chelate ligands is a proven method for counteracting hypomagnesemia. However, the coordination chemistry of such bio-relevant magnesium complexes is yet to be extensively explored or elucidated. It is the aim of this review to comprehensively describe what is currently known about common bio-relevant magnesium complexes from the perspective of coordination chemistry.
... Overall, some studies have reported the bioavailability of various Mg preparations [22][23][24], but comparative studies on the bioavailability of Mg from the different pharmaceutical formulations are lacking. In our study, MgC was given as granules for oral solution, and so Mg was dissolved and therefore in its ionized form when ingested. ...
Assessment of bioavailability of Mg from Mg citrate and Mg oxide by measuring urinary excretion in Mg-saturated subjects
Article
Full-text available
Background: Low magnesium (Mg) levels are linked to many diseases. Studies suggest that organic salts of Mg are more readily bioavailable than its oxide or inorganic salts used for supplements production. Unfortunately, the plethora of variables in the previous study designs complicates the making of any clear and reliable conclusions. Methods: 14 healthy males were supplemented for five days with 400 mg Mg to saturate Mg pools before intake of the test products. Bioavailability of 400 mg Mg from Mg citrate (MgC) and Mg oxide (MgO) after single-dose administration was assessed by measuring renal Mg excretion in 24-h urine and blood plasma [Mg] at time points 0, 2, 4, 8, and 24 h. Results: Single-dose MgC supplementation led to a significant (P < 0.05) increase in 24 h urinary Mg excretion, but this was not significant following MgO. Plasma [Mg] was also significantly higher for MgC than for MgO at 4 h (P < 0.05) and 8 h (P < 0.05). Compared with baseline levels, MgC supplementation showed a significant increase in plasma [Mg] at all time points, in contrast to MgO. Conclusions: MgC shows higher bioavailability compared with MgO. Furthermore, urinary Mg excretion should be determined as the primary endpoint of Mg bioavailability studies.
Bioavailability of magnesium food supplements: A systematic review
Article
Introduction: The market for food supplements is booming due to their increased consumption. European regulations include different ways in which vitamins/minerals are administered, without the consumer being clear if one formulation has advantages over the other. The aim was to compare the bioavailability of different forms of Mg and to analyze the differences between them. Methods: Based on a PICO (Population, Intervention, Comparison, Outcome) research question, a search strategy for Mg bioavailability studies that compared different forms was established for Pubmed, Cochrane, Web Of Science and Scopus databases. 433 studies were found of which 14 were finally selected. Results: Inorganic formulations appear to be less bioavailable than organic and the percentage of absorption is dose dependent. Conclusion: All Mg dietary supplements can maintain the physiological levels of Mg in healthy subjects without prior deficit, although it cannot be assured in older patients, patients with illnesses or with previous sub-physiological levels.
Agents affecting volume and composition of body fluids
Article
  • Jan 1980
Errata: Use of Ranks in One-Criterion Variance Analysis
Article
  • Dec 1952
Given C samples, with ni observations in the ith sample, a test of the hypothesis that the samples are from the same population may be made by ranking the observations from from 1 to Σni (giving each observation in a group of ties the mean of the ranks tied for), finding the C sums of ranks, and computing a statistic H. Under the stated hypothesis, H is distributed approximately as χ(C – 1), unless the samples are too small, in which case special approximations or exact tables are provided. One of the most important applications of the test is in detecting differences among the population means.** Based in part on research supported by the Office of Naval Research at the Statistical Research Center, University of Chicago.
CRC Handbook of Chemistry and Physics
Article
Magnesium status of alcoholic patients
Article
Ten chronic alcoholic patients ingesting at least 120 ml ethanol a day for 12 mo or more were examined, on ethanol withdrawal, for evidence of magnesium deficiency. Nine patients were found to have diminished skeletal-muscle magnesium values, their mean being significantly lower (p < 0.001) than that of normal controls. Retention of infused magnesium was well correlated with increment of magnesium values on repletion. All nine patients exhibited clinical features which might be attributed to magnesium deficiency, and which subsided during the course of magnesium therapy. None of the patients, however, had abnormal bone magnesium values, only two had low serum (total and ultrafiltrable), and one had a low erythrocyte, magnesium level.
A pharmacological method of measuring mouth caecal transit time in man
Article
  • Nov 1979
High-Performance Liquid Chromatographic Assay of Sulfapyridine and Acetylsulfapyridine in Biological Fluids
Article
  • Sep 1978
A high-pressure liquid chromatographic method for the sensitive, rapid, and specific determination of sulfapyridine and its N-acetyl derivative in plasma and saliva was developed. A cyano-bonded, reversed-phase, high efficiency column was used. The system detected these sulfonamides in serum to 0.25 mg/liter and within only 6 min. Sulfapyridine was separated from its acetyl derivative with little interference from other drugs. The assay reproducibility was within 3%. The assay was highly useful for routine monitoring of patients receiving sulfasalazine for inflammatory bowel disease.
Magnesium Depletion During Prolonged Fasting of Obese Males
Article
  • Nov 1969
Human Pharmacology Institute (HPI) Ciba-Geigy GmbH Waldh
  • Cleveland
  • B Crc Press
  • M D Mfihlbauer
Cleveland, CRC Press, B-106 B. Mfihlbauer, M. D. Human Pharmacology Institute (HPI) Ciba-Geigy GmbH Waldh/Srnlestrage 22 W-7400 Tt~bingen, FRG
Agents affecting volume and com-position of body fluids The pharmacological basis of therapeutics 8th ed., Perga-mon Bioavailability of magnesium
  • Jan 1990
  • 682-707
  • Mudge Gh
  • Weiner
  • Mt~hlbauer
Mudge GH, Weiner IM (1990) Agents affecting volume and com-position of body fluids. In: Gilman AG, Rall TW, Nies AS, Taylor P (eds) The pharmacological basis of therapeutics 8th ed., Perga-mon, New York, pp 682-707 B. Mt~hlbauer et al.: Bioavailability of magnesium
Agents affecting vo lum e and composition of body fluids (eds) The pharmacological basis of th erapeutics
  • Jan 1990
  • 682-707
  • Gh Mudge
  • Im Wein Er
Mudge GH, Wein er IM (1990) Agents affecting vo lum e and composition of body fluids. In: Gilman AG, Ra ll TW, Nies AS, Taylor P (eds) The pharmacological basis of th erapeutics 8th ed.. Perga mon, New York, pp 682-707