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Bioavailability of Magnesium Salts – A Review
Abstract
Background: Magnesium supplementation is of value in several different medical disorders. Several kinds of Mg-salts are commercially available. Purpose: This review evaluates their bioavailability criteria such as solubility, urinary excretion, and plasma levels of magnesium from studies of different Mg-salts. Conclusion: Although methodology differences were large, the results consistently demonstrate a better bioavailability for Mg-citrate.
... The water solubility of an Mg salt is important for its bioavailability. Organic Mg salts (for instance, citrate, gluconate, lactate and aspartate) have a higher water solubility than inorganic salts (for instance oxide and chloride), resulting in a greater intestinal absorption 22,50,51 . In spite of the lack of studies in stone formers, studies in healthy volunteers found that the urinary excretion of Mg increases more significantly after administration of one of the organic Mg salts (citrate, lactate and aspartate, were tested) than with Mg oxide 22,51 . ...
... Organic Mg salts (for instance, citrate, gluconate, lactate and aspartate) have a higher water solubility than inorganic salts (for instance oxide and chloride), resulting in a greater intestinal absorption 22,50,51 . In spite of the lack of studies in stone formers, studies in healthy volunteers found that the urinary excretion of Mg increases more significantly after administration of one of the organic Mg salts (citrate, lactate and aspartate, were tested) than with Mg oxide 22,51 . However, even a relatively insoluble Mg salt can reduce oxalate absorption. ...
Stone formers have lower urinary magnesium than healthy people. Higher urinary magnesium levels are associated with lower incidence of kidney stones, and hypomagnesuria has been described as a lithogenic risk factor. Magnesium can have direct and indirect inhibitory effects on lithogenesis: decreasing the absorption of oxalates in the intestine; forming magnesium oxalate complexes which reduces the saturation of calcium oxalate; increasing the urinary citrate and inhibiting the conversion of the calcium oxalate in its monohydrated form. Oral supplementation with magnesium is an effective way to correct hypomagnesuria. However, oral magnesium supplementation in recurrent stone formers with hypomagnesuria is still a subject of ongoing debate, and physicians treating these patients underestimate its potential preventive effects. Oral magnesium supplementation can be used as an adjuvant therapy to the standard prophylactic therapy, mainly in association with an alkali salt. It is well tolerated and has few adverse effects.
... The organic sources of magnesium, on the other hand, offer high levels of solubility, but provide limited levels of elemental magnesium (e.g., Mg citrate). Studies on the bioavailability of different magnesium salts consistently demonstrate that organic salts of magnesium (e.g., Mg citrate) have a higher bioavailability than inorganic salts (e.g., Mg oxide) [19]. This finding was also confirmed by a recent study in which both urinary excretion and serum levels of magnesium were significantly higher after single-dose administration of these two supplements in a randomized cross-over study design [20]. ...
... Moreover, reproducible baseline serum magnesium levels were found between different test days. The serum levels of magnesium express a circadian variation of around 6% [19,25]. This is confirmed in phase A of the current in vivo trial after placebo supplement ingestion, for which an average maximal increase of 4.8% (maximal value compared to the baseline value) was found throughout the timeframe of serum collection. ...
Despite the presumption of the beneficial effects of magnesium supplementation, little is known about the pharmacokinetics of different magnesium formulations. We aimed to investigate the value of two in vitro approaches to predict bioavailability of magnesium and to validate this in subsequent in vivo testing. In vitro assessment of 15 commercially available magnesium formulations was performed by means of a Simulator of the Human Intestinal Microbial Ecosystem (SHIME®) and by dissolution tests. Two magnesium formulations with contrasting bioavailability prediction from both in vitro tests (best vs. worst) were selected for in vivo testing in 30 subjects. In vivo bioavailability was compared following one acute ingestion by monitoring blood magnesium concentrations up to 6 h following intake. The in vitro tests showed a very wide variation in absorption and dissolution of the 15 magnesium products. In the in vivo testing, a significant different serum magnesium absorption profile was found up to 4 h following supplement ingestion for the two supplements with opposing in vitro test results. Moreover, maximal serum magnesium increase and total area under the curve were significantly different for both supplements (+6.2% vs. +4.6% and 6.87 vs. 0.31 mM.min, respectively). Collectively, poor bioaccessibility and bioavailability in the SHIME model clearly translated into poor dissolution and poor bioavailability in vivo. This provides a valid methodology for the prediction of in vivo bioavailability and effectiveness of micronutrients by specific in vitro approaches.
... Weitverbreitet ist die These, dass Magnesium aus organischen Verbindungen per se "die bessere" Salzform darstelle, da nur bestimmte organische Salze ausreichend absorbierbar seien und folglich bevorzugt verabreicht werden sollten [22,23]. ...
... 23] und hat sogar bereits Gerichte beschäftigt[19]. Deutlich ist, dass verschiedene Studien zu variierenden Ergebnissen gelangen, weil die Absorption von Magnesium durch eine Vielzahl von Faktoren beeinflusst wird, die aus methodischen Gründen nur teilweise in den Humanstudien abgebildet werden können. ...
... Vitamin A in cucumbers can also help reduce wrinkles and make skin appear softer. [11][12][13] [14][15][16] In addition, cucumbers can also reduce excess oil production on the face. Vitamin C contained in cucumbers can help prevent damage to skin cells from sunlight, thereby preventing premature aging. ...
Background. Cucumber is one of the natural ingredients that has been widely used traditionally to maintain facial skin health. Cucumber is rich in antioxidants which have the potential to suppress the inflammatory process that arises due to hormonal imbalances in melasma sufferers due to the use of injectable contraception. This study aimed to determine the effect of using a cucumber mask on the incidence of melasma in acceptors injection contraception users at the independent midwife practice in Bungursari, Purwakarta, Indonesia. Methods. This study was an experimental study in which a total of 30 research subjects participated in this study. Data analysis was carried out using SPSS 25 software in a bivariate manner to determine the effect of using cucumber masks on melasma. Results. After using the cucumber mask on the first day, there was an improvement in melasma in the intervention group compared to before using the cucumber mask, p=0.02 (p<0.05). Likewise, after using the cucumber mask on the second to the seventh day, there was an improvement in melasma in the intervention group compared to before using the cucumber mask, p <0.05. Conclusion. There is an effect of using a cucumber mask on melasma in acceptors of injection contraception users at the independent midwife practice in Bungursari, Purwakarta, Indonesia.
... Vitamin A in cucumbers can also help reduce wrinkles and make skin appear softer. [11][12][13] Cucumber also contains minerals such as [14][15][16] In addition, cucumbers can also reduce excess oil production on the face. Vitamin C contained in cucumbers can help prevent damage to skin cells from sunlight, thereby preventing premature aging. ...
Cucumber is one of the natural ingredients that has been widely used traditionally to maintain facial skin health. Cucumber is rich in antioxidants which have the potential to suppress the inflammatory process that arises due to hormonal imbalances in melasma sufferers due to the use of injectable contraception. This study aimed to determine the effect of using a cucumber mask on the incidence of melasma in acceptors injection contraception users at the independent midwife practice in Bungursari, Purwakarta, Indonesia. This study was an experimental study in which a total of 30 research subjects participated in this study. Data analysis was carried out using SPSS 25 software in a bivariate manner to determine the effect of using cucumber masks on melasma. After using the cucumber mask on the first day, there was an improvement in melasma in the intervention group compared to before using the cucumber mask, p=0.02 (p<0.05). Likewise, after using the cucumber mask on the second to the seventh day, there was an improvement in melasma in the intervention group compared to before using the cucumber mask, p <0.05. In conclusion, there is an effect of using a cucumber mask on melasma in acceptors of injection contraception users at the independent midwife practice in Bungursari, Purwakarta, Indonesia.
... Data from in-vitro studies suggest that magnesium bisglycinate can be absorbed through dipeptide absorption pathways in the upper part of the small intestine [12]. Magnesium citrate was chosen because, in addition to its better absorption than inorganic salts [13,14], it is known to bind to oxalates in the intestinal tract, thereby decreasing its absorption and accumulation in the body. Since most kidney stones are calcium oxalate, reducing the oxalate content in the body has been found to decrease the risk of nephrolithiasis [15][16][17], a common occurrence in FHHNC. ...
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive disorder affecting <1/1,000,000 people. It is caused by mutations in the CLDN16 (FHHNC Type 1) or CLDN19 (FHHNC Type 2) genes, which are located on Chromosomes 3q27 and 1p34.2, respectively. There are no drug therapies for this condition. Although magnesium salts represent an important class of compounds and exhibit various therapeutic actions as a supplement for magnesium deficiency in FHHNC, various formulations on the market have different bioavailability. We report the case of a patient with FHNNC first treated, in our Pediatric Institute, with high doses of magnesium pidolate and magnesium and potassium citrate. The patient began to neglect this therapy after experiencing frequent daily episodes of diarrhoea. Our pharmacy received a request for an alternative magnesium supplement that would better comply by ensuring a good magnesium intake which will result in adequate blood magnesium levels. In response, we developed a galenic compound in the form of effervescent magnesium. Here, we report on the promise of this formulation not only for better compliance than pidolate, but also for better bioavailability.
... Though oral magnesium supplementation is convenient for patients, use can often result in substantial gastrointestinal complications and e cacy may be limited by absorption. Therefore, patients who receive CNIs after allo-HCT require frequent intravenous (IV) magnesium replacement [5][6][7]. ...
Purpose Calcineurin inhibitor use after allogeneic hematopoietic cell transplantation (allo-HCT) is associated with significant magnesium wasting. Utilization of a prolonged magnesium infusion is thought to lead to a lower serum peak concentration and therefore, decreased renal wasting of magnesium. In November 2017, our institution implemented a modification to our inpatient electrolyte replacement protocol for allo-HCT recipients that extended the magnesium infusion rate from 4 g/2 h to 4 g/4 h based on this theoretical advantage.
The primary objective of this study was to compare the median magnesium requirements per day of admission between patients who received magnesium 4 g/2 h to patients who received magnesium 4 g/4 h. Secondary objectives included a comparison of the per-patient median serum magnesium concentration during admission, as well as the median incremental difference in serum magnesium concentration after intravenous replacement per patient per admission.
Methods: Allo-HCT recipients who received prolonged infusion magnesium infusions were compared to a historical cohort of allo-HCT patients who received shorter IV magnesium infusions. Admissions were included if the patient had received an allo-HCT within 100 days prior, was admitted to the Transplant and Cellular Therapy Unit at WVU Medicine J.W. Ruby Memorial Hospital and received at least one magnesium infusion and one dose of cyclosporine or tacrolimus. Admissions were excluded if the patient received oral magnesium, total parenteral nutrition, aminoglycosides, amphotericin, carboplatin, cisplatin, or foscarnet.
Results: The pre-implementation group consisted of 81 admissions (n=64 patients), while the post-implementation group consisted of 90 admissions (n=60 patients). Median magnesium requirements per day of admission were not different between groups at 1.4 grams of magnesium in the pre-implementation group and 1.9 grams of magnesium in the post-implementation group (P = 0.25). Median serum magnesium concentrations and median incremental difference in serum magnesium concentration after intravenous replacement were also not different between groups; 1.65 mg/dL vs 1.60 mg/dL (P = 0.65) and 0.30 mg/dL vs 0.28 mg/dL (P = 0.67), respectively.
Conclusions: Prolonged infusion of magnesium in allo-HCT recipients receiving CNI therapy does not result in improvement in magnesium retention.
... Jak wynika z przeprowadzonych dotychczas badań porównawczych, optymalne w uzupełnianiu niedoborów są preparaty zawierające organiczne sole magnezu, tj. cytrynian czy mleczan [11,54,55]. Celowe jest również łączenie preparatu magnezu z witaminą B 6 [6,11]. ...
[PL] Magnez jest jednym ze składników mineralnych niezbędnych do prawidłowego rozwoju i funkcjonowania organizmu człowieka. Bierze udział m.in. w pracy nerwów i mięśni, pobudliwości serca, utrzymaniu prawidłowego ciśnienia tętniczego krwi, integralności kości oraz w metabolizmie glukozy i insuliny. Niedobór magnezu wiąże się z większą podatnością na negatywne skutki stresu oraz z wieloma przewlekłymi chorobami, w tym migrenowymi bólami głowy, incydentami sercowo-naczyniowymi (zawał serca, udar mózgu), nadciśnieniem tętniczym, cukrzycą typu 2. Niniejsza praca przedstawia m.in. najnowsze badania w dziedzinie magnezu i chorób przewlekłych, źródła występowania magnezu w pożywieniu oraz możliwości jego suplementacji.
Słowa kluczowe: magnez, suplementacja, niedobór magnezu
[ENG] Magnesium is one of the minerals necessary for the proper functioning of the human body, which is essential for the regulation of muscular contraction, nerve transmission, cardiac excitability, blood pressure, bone integrity, and glucose insulin metabolism. Therefore, magnesium deficiency is associated with stressful conditions and many chronic diseases, including migraine headaches, cardiovascular incidents (heart attack, stroke), hypertension, and type 2 diabetes. This review presents recent research in the areas of magnesium and chronic disease, miscellaneous sources of magnesium in food, and the possibilities of its supplementation.
... Naopak, soli horčíka s organickými kyselinami (napr. askorbát, citran, orotát, aspartát, glycinát horečnatý) sú dobre rozpustné a v štúdiách sa preukazuje ich lepšia bio logická dostupnosť v porovnaní s anorganickými zlúčeninami [10,11]. Dobrá rozpustnosť v mieste vstrebávania je kľúčová pre dobrú bio logickú dostupnosť horčíka, lebo umožňuje uvoľnenie jeho dvojmocných katiónov, ktoré sa môžu vstrebať v čreve pasívnym aj aktívnym mechanizmom. ...
Cielená suplementácia horčíka, či už z dôvodu jeho nedostatočného nutričného príjmu, alebo aj z dôvodov terapeutických indikácií, je v praxi bežná. Pre účinné vstrebávanie iónov horčíka (Mg2+) pri jeho suplementácii je nevyhnutnou podmienkou dobrá rozpustnosť chemickej zlúčeniny. Je známe, že organické zlúčeniny horčíka majú lepšiu rozpustnosť než jeho anorganické zlúčeniny. Výber preparátu na dosiahnutie požadovaného efektu suplementácie horčíka je však často založený na empírii, pričom chýbajú dôkazy o farmakokinetike jednotlivých prípravkov s obsahom horčíka, ktoré by jednoznačne preukazovali biologickú dostupnosť magnézia vzhľadom na rôznu chemickú zlúčeninu horčíka v jednotlivých komerčných prípravkoch. Veľmi prínosnú štúdiu v tomto smere publikovala v roku 2019 skupina z Belgicka, v ktorej autori hodnotili 15 rôznych komerčne dostupných prípravkov s obsahom horčíka (v statuse liekov a výživových doplnkov) dvoma prístupmi in vitro a následne testami in vivo na dobrovoľníkoch. Štúdia potvrdila lepšiu, ale rozdielnu biologickú dostupnosť jednotlivých organických zlúčenín magnézia a zároveň overila validnosť metodológie založenej na testoch in vitro, ktoré umožňujú predikovať biologickú dostupnosť Mg2+ in vivo. Dihydrát magnézium orotát v štúdii preukázal najvyššiu absorpciu v simulovanom prostredí tenkého čreva in vitro a výborné disolučné parametre in vitro. V praxi je vhodné používať také prípravky horčíka, pri ktorých sa preukázala výborná biologická dostupnosť presvedčivými dôkazmi.
Targeted magnesium supplementation, either because of its insufficient nutritional intake or therapeutic indications, is common in practice. Good solubility of the chemical compound is a prerequisite for efficient absorption of magnesium ions (Mg2+) during its supplementation. It is known that organic magnesium compounds have better solubility than its inorganic compounds. However, choosing the appropriate magnesium formulation in order to achieve a desired effect of magnesium supplementation is often empirical and there is a lack of evidence of the pharmacokinetics of individual magnesium-containing formulations that would clearly demonstrate the bioavailability of different commercial formulations with respect to different magnesium compounds. A very beneficial study in this regard was published in 2019 by a team from Belgium, in which the authors evaluated 15 different commercially available magnesium-containing formulations (available as medicines and dietary supplements) by two in vitro approaches and subsequent in vivo tests on volunteers. The study confirmed better, but different,
bioavailability of individual organic magnesium compounds, and at the same time, the study verified the validity of the methodology based on in vitro tests. These findings allow to predict in vivo bioavailability of Mg2+. Dihydrate magnesium orotate demonstrated the
highest absorption in an in vitro simulated small intestinal environment and excellent in vitro dissolution parameters in the study. Magnesium formulations with excellent bioavailability confirmed by convincing evidence should be recommended in practice.
... Several products are available in the market to manage magnesium deficiency. These products consist of different salts that, as a consequence, lead to different bioavailability profiles [3]. Other pharmaceutical ingredients such as vitamins and other minerals are usually added to magnesium supplements [1,4]. ...
Objective: A new application of Atomic Absorption Spectroscopy (AAS) has been carried out to determine magnesium in its solid preparations (effervescent and uncoated compressed tablets) as an active ingredient and/or excipient. Methodology: The linear range of magnesium was determined. A sample of magnesium effervescent tablets was analyzed. Magnesium stearate concentration was also indirectly determined in commercial paracetamol tablets using two digestion methods. Finally, a sample of drug-free tablets (only contain excipients) was analyzed to study the effect of talc on total magnesium content of the sample. Results: Linear range was observed in concentrations between 0.08-0.40 ug/mL of magnesium. Effervescent tablets samples were recovered in the range between 98.66-103.00% which indicates that the product meets specifications. For paracetamol tablets, the content of magnesium stearate was in average of 0.2% and there is no differences between the two digestion methods (t=0.454). Our work on the drug-free sample proved a significant increase of magnesium concentrations in the presence of talc. Conclusion: The AAS method is a simple and rapid technique that can be employed for the simultaneous estimation of magnesium in in-process and final products analyses.
... Navyše sa musia solubilizovať v kyslom prostredí žalúdka, preto vyžadujú funkčný gastrointestinálny trakt [28]. Organické soli horčíka majú oveľa lepšiu rozpustnosť a hoci obsahujú nižšie množstvo elemen tárneho magnézia, ich bio logická do stupnosť magnézia je vysoká [29,30]. ...
U stavovcov, vrátane človeka, je mag-nézium štvrtý najzastúpenejší katión (Ca 2+ , Na + , K + , Mg 2+) a druhý najzastú-penejší intracelulárny katión (K + , Mg 2+). Je kofaktorom pre viac ako 300 enzy-matických reakcií, z ktorých mnohé za-hŕňajú tvorbu adenozíntrifosfátu. Mag-nézium reguluje transmembránový transport iných iónov, vrátane vápnika a draslíka, stabilizuje sekundárne štruk-túry DNA a RNA, zaisťuje normálnu sva-lovú kontrakciu a relaxáciu, srdcový rytmus, cievny tonus, neurologické funkcie a proliferáciu buniek [1]. Živý or-ganizmus, aj ľudský, optimálne funguje len pri zachovanej homeostáze všetkých makro-a mikronutientov. Homeostáza magnézia, nevyhnutná pre všetky pro-cesy, ktorých sa magnézium zúčastňuje, je výsledkom dynamickej rovnováhy medzi príjmom a resorpciou magné-zia z potravy, jeho uvoľňovaním z kosti, jeho zmien medzi intra-a extracelulár-nym kompartmentom a jeho vylučova-ním obličkami [2,3]. Pre človeka dnešných čias sa stáva ty-pickým, že jeho organizmus sa nachádza v stave energetického nadbytku, ale zá-roveň chronického nedostatku mikro-elementov, vrátane magnézia. Tento stav sa označuje ako subklinický, "tichý" nedostatok, ktorý dlhodobo pretrváva bez typických vonkajších prejavov, avšak s devastačným účinkom na bunkovej úrovni. Na tomto podklade postupne dochádza k rozvoju procesov, vedúcich k chronickým ochoreniam a iným zdra-votným poruchám [4]. Odhaduje sa, že v rozvinutých krajinách trpí subklinic-kým nedostatkom magnézia 10-30 % populácie [5]. Najčastejšou príčinou ne-dostatku magnézia je jeho deficit. Môže byť spôsobený buď nedostatočným prí-jmom, zvýšenou potrebou alebo zvý-šenou exkréciou magnézia obličkami (tab. 1) [6,7]. Nedostatok magnézia môže spôsobovať aj jeho deplécia, čo je poru-cha regulácie jeho homeostázy. Magnézium potrebujeme neustále prijímať z potravy, výborným zdrojom je pitná voda, pokiaľ má optimálne mi-nerálne zloženie najmä s ohľadom na obsah magnézia, kalcia a celkovú tvr-dosť. Bola publikovaná práca, ktorá preukázala spojitosť medzi nedostatoč-ným obsahom týchto minerálov v dô-sledku rôzneho geografického zloženia podzemných vôd a zdravotnými para-metrami obyvateľstva na Slovensku. Nízky obsah magnézia, vápnika a ich spoločné zastúpenie (Mg 2+ a Ca 2+) kore-lovali s vyššou úmrtnosťou na kardiovas-kulárne, onkologické a iné ochorenia [8]. Vo väčšine populácie sa celkový príjem magnézia za posledné desaťročia v dô-sledku životného štýlu, spracovania po-travín aj postupov v poľnohospodárstve Súhrn Magnézium je esenciálny minerál zahrnutý do početných fyziologických procesov každej bunky. Epidemiologické štúdie potvrdzujú, že veľká časť populácie je v stave subklinického nedostatku magnézia, ktorý sa spája s kardiovaskulárnymi, neurologickými a gynekolo-gickými poruchami. Lekárnik má možnosť aktívne riadiť suplementáciu magnéziom pri prevencii jeho deficitu, ako aj pri ochoreniach, ktoré sú s deficitom magnézia spojené. Na perorálnu suplementáciu sú vhodné organické soli magnézia, ktoré majú dobrú rozpustnosť vo vode. Nižšie jednorazové dávky magnézia podávané 2-3-krát denne umožňujú vyššiu resorpciu magnézia bez nežiaducich laxa-tívnych účinkov. Klinické zlepšenie vyžaduje dlhodobú suplementáciu. Pri výbere vhodného lieku je potrebné vziať do úvahy limitácie vyplývajúce zo zloženia rôznych liekov (vitamín B6, sodík, draslík). Kľúčové slová magnézium-suplementácia-deficit-lekárnik Summary Magnesium in the practice of a pharmacist. Magnesium is an essential mineral involved in numerous physiological processes of every cell. Epidemiological studies confirm that a large part of the population is in a state of subclinical magnesium deficiency, which is associated with cardiovascular, neurological and gynaecological disorders. A pharmacist can actively manage magnesium supplementation in preventing magnesium deficiency, as well as in diseases which are associated with magnesium deficiency. Organic magnesium salts with good water solubility are suitable for oral supplementation. Lower single doses of magnesium given 2-3 times a day allow a higher absorption of magnesium without adverse laxative effects. Clinical improvement requires long-term supplementation. When choosing a suitable drug, it is necessary to consider the limitations resulting from the composition of different drugs (vitamin B6, sodium, potassium).
... A 13 day cross-over pharmacokinetic study was performed in male Wistar rats to overcome interanimal variability using magnesium citrate as standard (since it is considered as best among all available salt of magnesium [23]). Animals were kept on initial 5 days saturation phase (administered with 100 mg/kg elemental magnesium as magnesium citrate through oral gavage) so as to ensure that they were not magnesium deficient. ...
... Mg can be delivered in an inorganic form, e.g., Mg oxide (MgO, oxide) or Mg carbonate (salt), or in an organic form, e.g., Mg citrate (MgC), Mg aspartate, Mg lactate, or Mg threonate (all organic salts). Various studies on the bioavailability of Mg have suggested that, in order to improve the Mg status of the individual, organic Mg salts are more effective than inorganic Mg compounds [8]. However, because of differences in methodological procedures and overall study design, the results from these studies are difficult to compare. ...
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.
... The studies demonstrate that organic Mg salts have a higher solubility than inorganic salts. 14,15 Several reagents in colorimetric as well as spectrophotometric methods for the determination of magnesium have been described in the literature, such as eriochrome black T (EBT), titan yellow (TY), ammonium phosphate method, ethylenediaminetetraacetic acid (EDTA), paratolyl-2-thenohydroxamic acid and quinalizarin, 4-methyl-3-((1-H-Indol-3-iyl)(phenyl)methyl)-1-H-Indol (MPBIM), and trizma-chloranilate. [16][17][18][19][20][21] All of these procedures require a true solution of a coloured magnesium complex in which the colour intensity is directly proportional to the magnesium concentration. ...
Magnesium is an essential element and the intracellular divalent cation involved in many biochemical functions. People with
magnesium deficiency must increase their intake of magnesium, usually in the form of various supplements. A common form
of magnesium supplement widely available in pharmacies is magnesium oxide (MgO). In this work, the content of MgO was
determined in pharmaceutical supplementations using spectrophotometry, based on the reaction between magnesium ions
and eriochrome black T at a wavelength of 535 nm. The analysed content of MgO ranged from 360.5 to 386.5 mg MgO, which
corresponds to the daily Mg recommended values (300 to 400 mg).
... Another study in 46 healthy volunteers also showed that magnesium oxide is suboptimally absorbed, and that magnesium citrate provides the highest plasma levels both acutely and at 60 days after administration 22 . Despite the heterogeneity of magnesium absorption studies, a review by Rylander 23 concluded, based on current evidence, that magnesium citrate is the most appropriate formulation for supplementation and other therapeutic purposes. In the present study, 100% of the respondents who specified the form of iv supplementation they used, said that they used magnesium sulfate. ...
Background:
The optimal management of hypomagnesemia (hMg) induced by epidermal growth factor receptor inhibitors (egfris) for advanced colorectal cancer is unclear. We surveyed gastrointestinal medical oncologists in Canada to determine practice patterns for the management of egfri-induced hMg.
Methods:
Based on distribution lists from the Eastern Canadian Colorectal Cancer Consensus Conference and the Western Canadian Gastrointestinal Cancer Consensus Conference, medical oncologists were invited to participate in an online questionnaire between November 2013 and February 2014.
Results:
From the 104 eligible physicians, 40 responses were obtained (38.5%). Panitumumab was more commonly prescribed than cetuximab by 70% of respondents, with 25% prescribing cetuximab and panitumumab equally. Most respondents obtain a serum magnesium level before initiating a patient on an egfri (92.5%) and before every treatment (90%). Most use a reactive strategy for magnesium supplementation (90%) and, when using supplementation, favour intravenous (iv) alone (40%) or iv and oral (45%) dosing. Magnesium sulfate was used for iv replacement, and the most common oral strategies were magnesium oxide (36.4%) and magnesium rougier (18.2%). Under the reactive strategy, intervention occurred at hMg grade 1 (70.3%) or grade 2 (27%). Of the survey respondents, 45% felt that 1-5 of their patients have ever developed symptoms attributable to hMg, and 35% have had to interrupt egfri therapy because of this toxicity, most commonly at grade 3 (30%) or grade 4 (45%) hMg. The most important question about egfri-induced hMg was its relevance to clinical outcomes (45%) and its symptoms (37.5%).
Conclusions:
In Canada, various strategies are used in the management of egfri-induced hMg, including prophylactic and reactive approaches that incorporate iv, oral, or a combination of iv and oral supplementation. Clinicians are concerned about the effect of hMg on clinical outcomes and about the symptoms that patients experience as a result of this toxicity.
... The study group was completely independent from the manufacturing company and had no conflicts of interest. Another important strength of the study is that Mg citrate was used for supplementation, with proven good bioavailability [35]. ...
Objective
To investigate the effect of magnesium (Mg) supplementation in healthy pregnant women for prevention of blood pressure increase. Secondary outcomes were comparison of biomarkers for hypertensive disorders and labour and fetal outcomes between the groups.
Methods
Two hundred nulliparous healthy pregnant women were double-blind randomized to receive Mg daily or placebo.
Results
There were no differences in blood pressure increase. However, among the Mg-treated women, there was a significant negative correlation between increase in blood levels of magnesium and increase in systolic blood pressure (p = 0.042). Magnesium supplementation seems to be safe for both mother and infant.
Conclusion
Magnesium supplementation in healthy first-time pregnant women is not to be recommended for prevention of blood pressure increase. Supplementation in risk pregnancies needs to be further investigated. The study is listed on the ISRCTN registry with study ID 13890849.
... The present results further support the general scientific opinion that the inorganic Mg compound Mg oxide is not as easily absorbable as organic Mg compounds [24]. Several studies showed that organic Mg compounds, such as Mg aspartate-hydrochloride or Mg lactate, generally have a higher bioavailability than Mg oxide [12,13]. ...
Background
The development of several disorders, such as cardiovascular diseases, diabetes and osteoporosis, has been linked to suboptimal dietary magnesium (Mg) intake. In this context, a number of studies have tried to investigate which Mg compounds are best suited for Mg supplementation. Results suggest that organic Mg compounds are superior to the inorganic Mg oxide in terms of bioavailability, but a reliable statement cannot yet be made due to systematic differences in the applied study designs.
Methods
This single-center, randomized, open, 2-period, 2-supplementation, 2-sequence, single-dose, cross-over study was conducted in 20 healthy male subjects of Caucasian origin to investigate and compare the bioavailability of Mg citrate, an organic Mg compound, and Mg oxide, an inorganic Mg compound. In order to reliably assess the bioavailability of both Mg compounds, subjects were supplemented with magnesium to saturate their Mg-pools before administration of each study product. The bioavailability of both Mg compounds was then assessed by measurement of the renally eliminated Mg quantity during an interval of 24 h after single-dose Mg administration (Ae 0-24h) as primary endpoint. Additionally, the Mg concentrations in a subset of leukocytes, in erythrocytes and in serum were measured on an exploratory basis.
Results
After administration, Ae 0-24h of magnesium was higher for Mg citrate than for Mg oxide. Ae 0-24h for both study products was compared by analysis of variance (ANOVA), revealing an adjusted mean difference of 0.565 mmol, which was statistically significant at the 5% level (95% confidence interval of 0.212 to 0.918 mmol, p = 0.0034). Besides, serum Mg concentrations were statistically significantly higher for Mg citrate than for Mg oxide at several time points after administration. No statistically significant difference was shown in intracellular Mg contents.
Conclusions
This study confirms former study results showing a higher bioavailability of the organic Mg compound Mg citrate compared to Mg oxide. It can be concluded that Mg citrate, similar to other organic Mg compounds, may be more suitable than Mg oxide to optimize the dietary magnesium intake.
Trial registration
Retrospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615001268538) on November 19, 2015.
Keywords
Bioavailability Oral Mg supplementation Mg citrate Mg oxide Urinary excretion
... Although in preclinical and clinical studies it was observed that organic Mg salts (e.g. acetate, pidolate, citrate, gluconate, lactate, aspartate) are better sources of Mg itself than inorganic Mg salts (MgO, MgCl 2 , MgSO 4 , MgCO 3 ) [20]; and a small analgesic inactive dose of two organic salts Values are means ± SEM; ** p < 0,01, *p < 0,05 normal magnesium lactate dihydrate vs magnesium micronized lactate dihydrate; ## p < 0,001 control vs normal magnesium lactate dihydrate;^^p < 0,001, control vs micronized magnesium lactate dihydrate. (i.e. ...
Purpose
As previously reported, magnesium sulphate administered parenterally significantly increased an opioid antinociception in different kinds of pain. Since the typical form of magnesium salts are poorly and slowly absorbed from the gastrointestinal tract we examined whether their micronized form could increase opioids induced antinociception.
Methods
In behavioural studies on rats morphine, tramadol and oxycodone together with magnesium (lactate dihydrate, hydroaspartate, chloride) in micronized (particles of size D90 < 50 μm) and conventional forms were used. Changes in pain thresholds were determined using mechanical stimuli. The intestinal absorption of two forms of magnesium lactate dihydrate (at the doses of 7.5 or 15 mg ions) in the porcine gut sac model were also compared.
Results
Micronized form of magnesium lactate dihydrate or hydroaspartate but not chloride (15 mg of magnesium ions kg⁻¹) enhanced the analgesic activity of orally administered opioids, significantly faster and more effective in comparison to the conventional form of magnesium salts (about 40% for oxycodone administered together with a micronized form of magnesium hydroaspartate). Moreover, in vitro studies of transport across porcine intestines of magnesium ions showed that magnesium salts administered in micronized form were absorbed from the intestines to a greater extent than the normal form of magnesium salts.
Conclusions
The co-administration of micronized magnesium organic salts with opioids increased their synergetic analgesic effect. This may suggest an innovative approach to the treatment of pain in clinical practice.
... The drug absorption depends on both the kind of Mg salt and other food elements that may either augment or abate it [15,16]. Nonetheless, documentation of their pharmacokinetic profiles remains sparse [17]. ...
Despite the presumption of a beneficial effect of magnesium (Mg) supplementation on various diseases, little is known concerning the pharmacokinetics of Mg hydroxide. This study was designed to provide a pharmacokinetic profile of Mg hydroxide after a single oral dose. Ten healthy male adults participated in this cross-over study with three 24-hr study days. Interventions were: 1) none (baseline), 2) oral intake of three (3 x 360 mg) tablets of Mg hydroxide (Mablet(®) ) and 3) IV bolus infusion of 2 g Mg sulphate (index drug). Blood samples were collected before the single dose, after (i.e. post treatment administration) 15, 30, 60, 90 and 120 min. - and after 3, 4, 6, 8, 12 and 24 hr. Urine was collected in four 6-hr periods per study day. Blood (N=10) and urine (N=6) Mg were analysed by descriptive statistics. Bioavailability was 14.9% (CI: 8.3; 26.8), blood clearance was 5.1 L/hr (CI: 2.1; 17.0), apparent volume of distribution was 60.2 L (CI: 35.6; 102.0), elimination constant was 0.08 hr(-1) (CI: 0.05; 0.14), half-life was 8.3 hr (CI: 4.8; 14.1), Cmax was 0.11 mmol/L (CI: 0.07; 0.14), and AUC(0-24) was 92.3 mmol/L x minutes (CI: 45.5; 139.1). Urine Mg excretion augmented by 17.7% (CI: 8.9; 35.0) from baseline. No severe side effects. Mg hydroxide demonstrates a 15% bioavailability, and it constitutes a clinically relevant option for oral Mg supplementation. No severe side effects were seen. This article is protected by copyright. All rights reserved.
... Nonetheless, in the majority of included RCTs the target population was either not selected according to baseline magnesium status, or was normomagnesemic. (3) Although we took into account the elemental magnesium dose prescribed , the bioavailability of magnesium salts is still important issue that could introduce bias, because organic salts have a higher solubility, absorption, and therefore, bioavailability than inorganic salts [67]. ...
A systematic review and meta-analysis was conducted to evaluate the effect of oral magnesium supplementation on insulin sensitivity and glucose control in both diabetic and non-diabetic individuals.
PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases were searched (from inception to November 25, 2015) to identify RCTs evaluating the effect of magnesium on insulin sensitivity and glucose control. A random-effects model and generic inverse variance method were used to compensate for the heterogeneity of studies. Publication bias, sensitivity analysis, and meta-regression assessments were conducted using standard methods.
The impact of magnesium supplementation on plasma concentrations of glucose, glycated hemoglobin (HbA1c), insulin, and HOMA-IR index was assessed in 22, 14, 12 and 10 treatment arms, respectively. A significant effect of magnesium supplementation was observed on HOMA-IR index (WMD: −0.67, 95% CI: −1.20, −0.14, _p_ = 0.013) but not on plasma glucose (WMD: −0.20 mmol/L, 95% CI: −0.45, 0.05, _p_ = 0.119), HbA1c (WMD: 0.018 mmol/L, 95% CI: −0.10, 0.13, _p_ = 0.756), and insulin (WMD: −2.22 mmol/L, 95% CI: −9.62, 5.17, _p_ = 0.556). A subgroup analysis comparing magnesium supplementation durations of <4 months versus ≥4 months, exhibited a significant difference for fasting glucose concentrations (_p_<0.001) and HOMA-IR (_p_ = 0.001) in favor of the latter subgroup.
Magnesium supplementation for ≥4 months significantly improves the HOMA-IR index and fasting glucose, in both diabetic and non-diabetic subjects. The present findings suggest that magnesium may be a beneficial supplement in glucose metabolic disorders.
... Of the various magnesium containing supplements, those containing organic magnesium compounds (esp. magnesium citrate) have been shown to be superior to anorganic magnesium salts [55]. ...
The essential mineral magnesium is involved in numerous physiological processes. Recommended dietary intake is often not met and a low magnesium status increases the risk for various diseases. Magnesium status is regulated by several magnesium transport systems either in cellular or paracellular pathways. Numerous drugs either interfere with magnesium absorption in the intestines or the reabsorption from primary urine in the kidney. Low magnesium status has been identified as a significant risk factor for several diseases, including type-2 diabetes, cardiovascular diseases, arrhythmias, as well as general muscular and neurological problems. Therefore, an adequate magnesium supply would be of special benefit to our overall health.
... Firoz i Graber udowodnili stosunkowo niską biodostępność tlenku magnezu, a równoważną biodostępność chlorku, mleczanu i asparaginianu magnezu [20]. Rylander przeprowadził szeroką metaanalizę i stwierdził, że cytrynian magnezu jest związkiem najbardziej wskazanym do suplementacji tego pierwiastka [21]. Tlenek magnezu jest wskazany u pacjentów z nadkwasotą i stanami zapalnymi żołądka. ...
Wstęp
Magnez jest jednym z makroelementów niezbędnych do zachowania prawidłowej homeostazy organizmu. Stwierdzono jego pozytywne działanie w profilaktyce chorób sercowo-naczyniowych, osteoporozy pomenopauzalnej i cukrzycy. Niestety, obserwuje się niedobory tego pierwiastka w codziennej diecie, dlatego wskazana jest jego suplementacja. Celem badań było określenie wpływu rodzaju związku magnezu na dostępność farmaceutyczną Mg2+ z tabletek o niemodyfikowanej szybkości uwalniania.
Materiał i metody
Do badań wykorzystano preparaty: Biomagnezja 150, Citromag B6 i Biomagnezja Plus (FZNP „Biochefa”). Badanie szybkości uwalniania substancji czynnej wykonano w aparacie łopatkowym w T = 37°C ± 0,5°C, w czasie 120 min, przy 50 obrotach mieszadła/min, stosując 0,1 mol/dm<sup>3</sup> HCl (pH = 1,2). Do analizy przebiegu uwalniania zastosowano program Statistica Zestaw Farmaceutyczny: Profile Uwalniania.
Wyniki
Analiza badanych preparatów wykazała, że procent uwolnionego magnezu wzrastał w kolejności: Biomagnezja Plus, Biomagnezja 150, Citromag B6 i wynosił odpowiednio: 45%, 61% i 70%. W takiej samej kolejności rosły stałe szybkości uwalniania: 0,0138 min<sup>-1</sup>; 0,0146 min<sup>-1</sup>; 0,018 min<sup>-1</sup>.
Wnioski
Czynnikami wpływającymi na uwalnianie magnezu w warunkach in vitro są rozpuszczalność związku, obecność nieorganicznego anionu lub organicznego liganda i trwałość związku. Im większa rozpuszczalność substancji, tym wyższy procent uwalniania. Obecność liganda organicznego (wodorocytrynianu) determinuje większy procent uwolnionej dawki magnezu w porównaniu z jego tlenkiem.
... Neueste Untersuchungen belegen zudem einen direkten positiven Zusammenhang zwischen der Serum-Mg-Konzentration und der Beinmuskelkraft bei gesunden jungen Männern [20]. [24]. Als einzige erwähnenswerte Nebenwirkung der oralen Mg-Therapie kann es infolge der wasserbindenden Wirkung von Mg im Darmtrakt zu Stuhlaufweichung kommen. ...
... (32,33) Previous intervention studies with Mg supplements found mixed effects on circulating hs-CRP but do not reflect the effects of diet because supplements consist of single compounds with variable bioavailability. (32,(34)(35)(36) Despite the biological plausibility that greater intakes of dietary Mg would be associated with improved skeletal muscle mass, grip strength, and power, to our knowledge there has only been one previous cross-sectional study that found a positive relationship between dietary Mg and appendicular lean mass but not grip strength. (37) Furthermore, no previous population study has examined the possible mediating effects of dietary Mg on inflammation in addition to its association with skeletal muscle mass, strength, and power. ...
Age-related loss of skeletal muscle mass and strength are risk factors for sarcopenia, osteoporosis, falls, fractures, frailty and mortality. Dietary magnesium (Mg) could play a role in prevention of age-related loss of skeletal muscle mass, power and strength directly through physiological mechanisms or indirectly through an impact on chronic low-grade inflammation, itself a risk factor for loss of skeletal muscle mass and strength. In a cross-sectional study of 2570 women aged 18-79 years we examined associations between intakes of Mg, estimated using an FFQ, DXA-derived measures of muscle mass (fat free mass as a percentage of body weight (FFM%), fat free mass index (FFMI, kg/m(2) )), leg explosive power (LEP) and grip-strength (n = 949 only). We also examined associations between circulating hs-CRP (C-reactive protein) and muscle mass and LEP, and explored the potential attenuation of these relationships by Mg. We compared our findings with those of age and protein intake. Endpoints were calculated by quintile of Mg and adjusted for relevant confounders. Significant positive associations were found between a higher Mg and indices of skeletal muscle mass and LEP, and also with hs-CRP, after adjustment for covariates. Contrasting extreme quintiles of Mg intake showed differences of 2.6% for FFM% (P trend <0.001), 0.4 kg/m(2) for FFMI (P trend = 0.005), and 19.6 watts/kg for LEP (P trend < 0.001). Compared to protein these positive associations were 7 times greater for FFM% and 2.5 times greater for LEP. We also found that higher hs-CRP was negatively associated with skeletal muscle mass and, in statistical modelling, that a higher dietary Mg attenuated this negative relationship by 6.5%, with greater attenuation in women aged over 50 years. No association was found between Mg and grip strength. Our results suggest that dietary magnesium may aid conservation of age-related loss of skeletal muscle mass and power in women of all ages. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Background and Aims
Optimal management of cancer treatment-induced hypomagnesemia (hMg) is not known. We assessed the feasibility of using a novel pragmatic clinical trials model to compare two commonly used oral Mg replacement strategies.
Methods
Patients with grade 1 to 3 hMg while receiving either platinum-based chemotherapy or epidermal growth factor receptor inhibitors (EGFRI) were randomized to oral magnesium oxide (MgOx) or oral magnesium citrate (MgCit). The trial methodology utilized the integrated consent model. Feasibility would be successful if; accrual rate was ≥5 patients a month and if measures of patient and physician engagement, were > 50%. Secondary endpoints included; comparison of Mg levels, cardiac arrhythmias, and rates of treatment delay/hospitalizations.
Results
From July 2016 to December 2017, an average of 1 patient a month was accrued. All 15 eligible and approached patients consented to participate in the study (100% engagement) and 7/15 were randomized to MgOx and 8/15 to MgCit. The percentage of physicians who approached patients for the study was 4 of 6 (66.6% engagement). The mean slope of change in Mg (mmol/L/day) was 0.0022 (95% CI: −0.0001 to 0.0044) for MgOx and 0.0006 (95% CI, −0.0012 to 0.0024) for MgCit (P = .2123). Three patients (20%) required IV magnesium while on the study (2 MgCit and 1 MgOx). Grade 1 diarrhea occurred in 3 patients in the MgCit arm.
Conclusion
Despite oral magnesium tolerability and meeting most of its feasibility endpoints, this study did not meet its target accrual rate. Alternative designs would be necessary for a definitive efficacy study.
Magnesium (Mg) deficiency may affect bone metabolism by increasing osteoclasts, decreasing osteoblasts, promoting inflammation/oxidative stress, and result in subsequent bone loss. The objective of the present study was to identify the molecular mechanism underlying the bone protective effect of different forms of Mg (inorganic magnesium oxide (MgO) versus organic magnesium picolinate (MgPic) compound) in rats fed with a high-fat diet (HFD). Forty-two Wistar albino male rats were divided into six group (n = 7): (i) control, (ii) MgO, (iii) MgPic, (iv) HFD, (v) HFD + MgO, and (vi) HFD + MgPic. Bone mineral density (BMD) increased in the Mg supplemented groups, especially MgPic, as compared with the HFD group (p < 0.001). As compared with the HFD + MgO group, the HFD + MgPic group had higher bone P (p < 0.05) and Mg levels (p < 0.001). In addition, as compared to MgO, MgPic improved bone formation by increasing the levels of osteogenetic proteins (COL1A1 (p < 0.001), BMP2 (p < 0.001), Runx2 (p < 0.001), OPG (p < 0.05), and OCN (p < 0.001), IGF-1 (p < 0.001)), while prevented bone resorption by reducing the levels of RANK and RANKL (p < 0.001). In conclusion, the present data showed that the MgPic could increase osteogenic protein levels in bone more effectively than MgO, prevent bone loss, and contribute to bone formation in HFD rats.
Over half of the adult population consumes dietary supplements, according to one estimate. Choosing the right form of supplements based on the physiology of the patient, genetic variability (if possible), and lifestyle factors are important. Some supplements have poor bioavailability based on the chemical nature of an ingredient. These products should either be combined with ingredients or processed in a way to enhance bioavailability. The supplement should be able to disintegrate and dissolve in a specific amount of time. Knowledge of inactive ingredients is recommended to avoid unintended side effects. Suggestions to assist in the supplement evaluation process are provided.
Magnesium is an essential nutrient that is involved in practically every major metabolic and biochemical process within the cell. The human body contains about 25 g of magnesium, with about 50%–60% in the bone and the remainder in soft tissue. Magnesium (Mg²⁺) is a divalent metal ion, the fourth most abundant cation in the body after calcium, potassium, and sodium. Food sources high in magnesium include green, leafy vegetables, unpolished grains, and nuts. Strong evidence suggests magnesium deficiency contributes to cardiovascular disease, the metabolic syndrome, type 2 diabetes, and osteoporosis. Magnesium status is difficult to measure but best defined by dietary intake coupled with serum magnesium concentrations and urinary magnesium excretion.
Background
High values of endogenous levels of magnesium (Mg) in the body and mechanisms of homeostasis regulation make it difficult to assess the bioavailability of these drugs. The aim of this study was to assess the Mg concentration in blood in volunteers and in erythrocytes in patients with hypomagnesemia.
Methods
The study included 20 healthy volunteers and 62 patients with chronic heart failure (CHF) I–III functional class (FC) NYHA classification. We studied the composition of Mgorotate and Mgorotate plus potassium (К)orotate. Blood sampling was carried out at 8 a.m. and within 10 h after administering the drugs. Measurement of Mg pharmacokinetic parameters: AUC (concentration of the active substance-time), and Cmax (maximum concentration) in volunteers and measurement of the concentration of Mg in erythrocytes of patients.
Results
The results indicated that both the AUC in volunteers and concentration of Mg in erythrocytes of patients are comparable, and the differences are not statistically significant.
Conclusions
The study showed that the standard method of calculating the AUC (total serum Mg) is insufficient for comparative evaluation of Mg absorption due to the high levels of its endogenous content and a small increase in concentration after taking the drugs. It is advisable to assess the concentration of Mg in the red blood cells of patients.
Magnesium is an essential element involved in various biochemical processes in the human body. In addition to oral supplementation, topical magnesium application is another conventional form of magnesium delivery for the treatment of skin diseases and muscle inflammation. Cucumber extract is a well-known superfood for human skin. It has been widely used in various skincare product lines because of its known benefits to the skin. The benefit of cucumber extract to the human skin would be significantly enhanced if the cucumber extract was fermented to convert the reducing sugars to beneficial organic acids. In this study, we developed a protocol for lactic acid fermentation of cucumber extract using hydromagnesite as a neutralizing agent. Various lactic acid bacteria were screened for fermentation of cucumber extract. The best fermenting performance was observed with Lactobacillus paracasei, which could convert approximately 13 g/L of reducing sugars (glucose and fructose) to lactic acid and a minor amount of acetic acid within 2 days of incubation. The final fermented cucumber extract contains magnesium in the form of salts of organic acids, which have high absorption ability and bioavailability. The product is a potent ingredient for producing dermal magnesium products.
In the past decade, significant progress has been made in understanding the medical threats posed by vascular calcification (VC). This recent development comes after a long history of misinterpreting this condition as a mere consequence of aging. As a result, there is presently no pharmacological treatment approved for the prevention or ablation of VC. Patients diagnosed with this chronic and debilitating condition are hence left at a great risk of experiencing serious cardiovascular events. Researchers, however, are ever better understanding the disease's pathophysiology, and promising avenues for drug development have emerged. In this review, recent clinical results of proposed calcification inhibitors are consolidated and selected investigational therapeutics are portrayed. Finally, opportunities for drug development approaches are highlighted and an objective account of challenges that remain in achieving this goal is provided.
Objective: To assess absolute bioavailability of 20 mEq Magnesium lactate extended release (ER) caplets and to assess the effect of food on the pharmacokinetics of these ER caplets.
Significance: Magnesium in different salt forms is available as over-the-counter oral formulations. The absorption and bioavailability is highly affected by water solubility of the salt form. A new ER caplet of 10 mEq strength of Magnesium L-lactate dihydrate has been developed to increase bioavailability of magnesium.
Methods: An open label, single dose, randomized, 3-period, cross-over study in healthy adults was conducted with three treatments: (A) single oral dose of 20 mEq magnesium L-lactate dehydrate under fasting conditions, (B) single intravenous (IV) infusion of 20 mEq magnesium sulfate and (C) single oral dose of 20 mEq magnesium L-lactate dehydrate under fed conditions. Urine and blood samples were collected for analysis of urinary and serum magnesium concentrations.
Results: Absolute bioavailabilities of the caplets under fasted and fed conditions, compared to IV magnesium sulfate, were 20.26% (fasted) and 12.49% (fed) in serum, based on the geometric mean ratio (GMR) of the baseline-adjusted AUC0-72, and 38.11% (fasted) and 40.99% (fed) in urine, based on the GMR of the baseline-adjusted Ae0-72. Relative bioavailability of the caplets comparing the fed and fasted states was 61.67% in serum, based on the GMR of the baseline-adjusted AUC0-72, and 107.57% in urine, based on the GMR of the baseline-adjusted Ae0-72.
Conclusions: This new magnesium formulation has reasonable bioavailability and might be a valuable addition to the currently available magnesium oral products.
In this review, we explore the role for intravenous magnesium sulfate (IVMg) to treat children with acute exacerbations of asthma. Children who receive care for severe acute asthma in emergency departments are often hospitalized after inadequate response to standard asthma treatment. IVMg may have a role to decrease hospitalization of children with severe acute asthma, but is in need of further research. Future exploration of IVMg should include larger randomized controlled trials of IVMg versus standard treatment, administration of IVMg with enough time to have effect on hospitalization, exploration of the pharmacology of IVMg so that the most effective dosage regimens can be selected, and use of measures and criteria to select research participants reflective of the children likely to benefit from more effective asthma treatment in clinical practice.
There is an abundance of data regarding the importance of magnesium (Mg) in a variety of human functions such as regulation of muscular tonus, insulin sensitivity, and cardio-vascular function [1-4]. In spite of this the results from intervention studies with the aim to ameliorate or prevent pathological processes in relation to these mechanisms remain less convincing. A meta-analysis of the effect of Mg on blood pressure concluded that there was no robust evidence that oral Mg supplementation reduces high blood pressure in adults [4]. It is likely that several of the intervention studies are influenced by method-ological problems. The aim of this review is to focus on some important such problems and suggest how they can be avoided in studies on intervention with Mg.
Magnesium is an important cation present in more than 300 enzymes in the body. This review evaluates the information on magnesium and pregnancy. In normal pregnancies Mg responsive genes are upregulated, suggesting Mg deficiency. Blood pressure increase is related to the urinary excretion of Mg. In pregnancies complicated by preeclampsia the Mg homeostasis is different from normal pregnancies. Supplementation with Mg has shown beneficial effects on high blood pressure and infant conditions in some studies. Although several studies show important relationships between Mg homeostasis and pregnancy, particularly those with pre-eclampsia, further studies are needed to assess the relationship and formulate requirements for intervention programmes.
Copyright © 2014 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.
The average magnesium uptake recommendation for an adult is in the range of 300 to 400 mg/day. During recent years dietary reference intakes in the USA and also in Germany/Austria/Switzerland have been slightly increased from the respective nutrition societies up to 400 mg/day for young men. The basis for these recommendations, among others, are balance studies. During the last years a series of balance and duplicate studies have been performed to determine magnesium uptake and balance in German and Mexican adults, in vegetarians, and in lactating women. In addition, the effect of supplementing a normal diet with 100 mg magnesium from a multimineral/multivitamin preparation was tested in a double blind, placebo controlled study in young women and in women during lactation. Daily magnesium intake from a self-selected diet in Germany was determined in duplicate studies in 1988/1992/1996 to be about 200 mg for women and 250 mg for men. Compared to these data a self-selected Mexican diet provided an average of 301 mg magnesium/day to women and 318 mg to men. Female and male vegetarians consumed 376 respective 474 mg magnesium/day. Balance studies that were performed over a period of 7 days showed no significant net uptake or net loss of magnesium. Supplementing the daily diet with 100 mg magnesium also did not lead to a changed balance. The higher intake was reflected by an increased urinary magnesium excretion, showing that about 20 to 40 % of the additional magnesium had been absorbed. Serum magnesium concentrations were not changed in young lactating and non-lactating women. In addition to these magnesium balance studies in various test populations it could be shown that during aging a significant amount of magnesium (up to 50 %) is lost from the bones which represents the main storage compartment for magnesium.
Purpose:
To assess if hypertension during the last part of pregnancy could be prevented by magnesium supplementation.
Methods:
Pregnant primagravida women from a local antenatal care unit were given an oral supply of 300 mg magnesium as citrate or placebo from pregnancy week 25 in a randomised double-blind setup. Blood pressure was recorded during pregnancy as well as pregnancy outcome.
Results:
In the magnesium-supplemented group, the average diastolic blood pressure at week 37 was significantly lower than in the placebo group (72/1.4 mean/SEM vs 77/1.4, p = 0.031). The number of women with an increase in diastolic blood pressure of ≥15 mmHg was significantly lower in the magnesium group compared with the women who received placebo (p = 0.011). There was an inverse relation between the urinary excretion of magnesium during pregnancy and the diastolic blood pressure (p = 0.005).
Conclusions:
Magnesium supplementation prevented an increase in diastolic blood pressure during the last weeks of pregnancy. The relation between diastolic blood pressure and urinary excretion of magnesium suggests that magnesium is involved in the regulation of blood pressure and that the increase in diastolic blood pressure in pregnancy could be due to a lack of magnesium.
Previous experimental studies demonstrate that the acid-base balance influences mineral homeostasis by regulating the absorption of calcium and magnesium in the kidneys. No intervention studies are available on population samples.
To study the urinary excretion of calcium and magnesium before and after an intervention with the aim of decreasing the acid load.
Healthy subjects aged 50-75 years were recruited by advertising. Urinary calcium, magnesium and urea as well as blood pressure were measured before and after the intervention. This comprised taking tablets containing potassium hydrogen carbonate or potassium chloride (placebo) during 7-10 days.
There were significant relationships between the urinary excretion of urea and magnesium and calcium before the intervention. Comparing before and after intervention, the change in urinary excretion of urea was related to a change in urinary excretion of calcium and magnesium. There was a significant decrease in systolic as well as diastolic blood pressure both after administration of potassium hydrogen carbonate and citrate.
The results confirm previous studies showing a relation between acid conditions in the body and the excretion of calcium and add new data on magnesium. A blood pressure decrease after potassium has been found in previous studies. This suggests an alternative for the treatment of moderately increased levels of blood pressure that should be further explored.
There are inconsistent findings about the efficacy of magnesium in the prophylaxis of migraine attacks and there is no study of magnesium prophylaxis focused on migraine subtypes without aura. In this double blind, randomized, placebo controlled study; we tried to evaluate the prophylactic effects of oral magnesium in migraine patients without aura. The prophylactic effects of 600 mg/day oral magnesium citrate supplementation were assessed by means of clinical evaluation, visual evoked potential and statistical parametric mapping of brain single photon emission computerized tomography before and after a 3 month treatment period. The results of 30 patients with migraine without aura (20-55 years old with 2-5 migraine attacks per month) on magnesium treatment were compared with those of 10 patients with similar properties on placebo treatment. Migraine attack frequency, severity and P1 amplitude in visual evoked potential examination decreased after magnesium treatment with respect to pretreatment values (p < 0.001). In a comparison of the effects of magnesium treatment with those of placebo, post/pretreatment ratios of migraine attack frequency, severity and P1 amplitude in Mg treatment group were found to be significantly lower than those in placebo treatment group (attack frequency p = 0.005, attack severity p < 0.001, P1 amplitude p < 0.05). Cortical blood flow in inferolateral frontal (p < 0.001), inferolateral temporal (p = 0.001) and insular regions (p < 0.01) increased significantly after magnesium treatment with respect to the pretreatment; while such significant changes of cortical blood flow were not observed with placebo treatment. These results have made us think that magnesium is a beneficial agent in prophylaxis of migraine without aura and might work with both vascular and neurogenic mechanisms.
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
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P (eds) The pharmacological basis of therapeutics 8th ed ., Pergamon,
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2. Drenick EJ , Hunt IF, Swcndscid ME ( 1969) Magnesium depletion
during prolonged fasting of obese males. J Cl in Endocrinol Metab
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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
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7. Weast RC (1975) Handbook of chemistry and physics, 55th ed.
Cleveland. CRC Press, B-106
The bioavailability of Mg from different preparations after oral intake has been evaluated by measuring the Mg elimination in 24-hour urine during placebo and treatment periods in 18 normal female students receiving 15-20.6 mmol/day. The urine elimination was increased 0.9-1.3 mmol/24 h by (a) tablets containing Mg citrate/Mg lactate 5 mmol three times a day; (b) tablets containing Mg citrate/Mg lactate and Mg hydroxide, 5 mmol three times a day; (c) tablets containing Mg hydroxide (Emgesan 10.3 mmol) twice a day; (d) solutions with Mg chloride (0.5 mmol/ml) 10 ml three times a day. There was no statistical difference in urine elimination after intake of the different preparations. The differences in Mg elimination/24 h discriminated between control and treatment groups just as well as or better than differences calculated on the basis of Mg/creatinine ratios.
Magnesium deficiency is seen with some frequency in the outpatient setting and requires oral repletion or maintenance therapy. The purpose of this study was to measure the bioavailability of four commercially-available preparations of magnesium, and to test the claim that organic salts are more easily absorbed. Bioavailability was measured as the increment of urinary maginesium excretion in normal volunteers given approximately 21 mEq/day of the test preparations. Results indicated relatively poor bioavailability of magnesium oxide (fractional absorption 4 per cent) but significantly higher and equivalent bioavailability of magnesium chloride, magnesium lactate and magnesium aspartate. We conclude that there is relatively poor bioavailability of magnesium oxide, but greater and equivalent bioavailability of magnesium chloride, lactate, and aspartate. Inorganic magnesium salts, depending on the preparation, may have bioavailability equivalent to organic magnesium salts.
Several previous epidemiological studies have shown a relation between drinking water quality and death in cardiovascular disease whereas others have not found such a relationship. An intervention study was undertaken to evaluate the effect of water with added magnesium and natural mineral water on blood pressure.
A group of 70 subjects with borderline hypertension was recruited and consumed 1) a water low in minerals, 2) magnesium enriched water or 3) natural mineral water, in a random, double blind fashion during four weeks.
Among persons with an initial low excretion of magnesium or calcium in the urine, the urinary excretion of magnesium was increased in the groups consuming the two waters containing magnesium after 4 weeks. A significant decrease in blood pressure was found in the group consuming mineral water at 2 and 4 weeks.
The results suggest that minerals taken in water are significant for the body burden and that an intake of mineral water among persons with a low urinary excretion of magnesium or calcium may decrease the blood pressure. Further studies should investigate the extent of mineral deficiency in different populations and the efficiency of different vehicles for supplying minerals, particularly magnesium and calcium.
The molecular biology of mammalian magnesium transporters and their interrelations in cellular magnesium homeostasis are largely
unknown. Recently, the mouse SLC41A1 protein was suggested to be a candidate magnesium transporter with channel-like properties
when overexpressed in Xenopus laevis oocytes. Here, we demonstrate that human SLC41A1 overexpressed in HEK293 cells forms protein complexes and locates to the
plasma membrane without, however, giving rise to any detectable magnesium currents during whole cell patch clamp experiments.
Nevertheless, in a strain of Salmonella enterica exhibiting disruption of all three distinct magnesium transport systems (CorA, MgtA, and MgtB), overexpression of human SLC41A1
functionally substitutes these transporters and restores the growth of the mutant bacteria at magnesium concentrations otherwise
non-permissive for growth. Thus, we have identified human SLC41A1 as being a bona fide magnesium transporter. Most importantly, overexpressed SLC41A1 provide HEK293 cells with an increased magnesium efflux capacity.
With outwardly directed Mg2+ gradients, a SLC41A1-dependent reduction of the free intracellular magnesium concentration accompanied by a significant net
decrease of the total cellular magnesium concentration could be observed in such cells. SLC41A1 activity is temperature-sensitive
but not sensitive to the only known magnesium channel blocker, cobalt(III) hexaammine. Taken together, these data functionally identify SLC41A1 as a mammalian carrier mediating magnesium efflux.
Intracellular Mg ²⁺ ([Mg ²⁺ ] i ) is overall well regulated, however it is not known whether Mg supplementation may lead to its acute changes. Therefore we examined acute effect of Mg administered either in form of MgO or Mg citrate on total plasma Mg ([Mg] p ) and [Mg ²⁺ ] i in human leukocytes.
Study design
51 healthy individuals were randomized into 3 groups. One group received 300 mg Mg as MgO (n = 20), another group received 300 mg Mg as Mg‐citrate (n = 21). A control group contained 10 persons. Samples were obtained at 0 h and 1, 3, 9, and 24 h after supplementation. Probands ingested the supplement after breakfast. All probands received identical food and table water containing low‐Mg during the sampling time. [Mg] p was determined by AAS. [Mg ²⁺ ] i was assessed as 340/380 nm mag‐fura 2 ratios in leukocytes of the probands.
Results
Significant changes in [Mg] p could not be observed between groups. However supplementation with Mg lead to a significant increase of 340/380 nm ratios after 3, 9, and 24 h. After 9 and 24 h, the 340/380 nm ratios were significantly higher for Mg‐citrate than for MgO.
Conclusion
Even though only minor changes in [Mg] p could be detected already 3 h after Mg supplementation [Mg ²⁺ ] i increased but returned to near normal after 24 h. Mg given as Mg‐citrate induced significantly higher increases of [Mg ²⁺ ] i as if given as MgO.
The magnesium content in food consumed in the Western world is steadily decreasing. Hypomagnesemia is associated with increased incidence of diabetes mellitus, metabolic syndrome, all-cause and coronary artery disease mortality. We investigated the impact of supplemental oral magnesium citrate versus magnesium oxide on intracellular magnesium levels ([Mg2+]i) and platelet function in healthy subjects with no apparent heart disease. In a randomized, prospective, double-blind, crossover study, 41 (20 women) healthy volunteers [mean age 53±8 (range 31-75) years] received either magnesium oxide monohydrate tablets (520 mg/day of elemental magnesium) or magnesium citrate tablets (295.8 mg/day of elemental magnesium) for one month (phase 1), followed by a four-week wash-out period, and then crossover treatment for one month (phase 2). [Mg2+]i was assessed from sublingual cells through x-ray dispersion (normal values 37.9±4.0 mEq/L), serum magnesium levels, platelet aggregation, and quality-of-life questionnaires were assessed before and after each phase. Oral magnesium oxide, rather than magnesium citrate, significantly increased [Mg2+]i (34.4±3 versus 36.3±2 mEq/L, p<0.001 and 34.7±2 versus 35.4±2 mEq/L, p=0.097; respectively), reduced total cholesterol (201±37 versus 186±27 mg/dL, p=0.016 and 187±28 versus 187±25 mg/dL, p=0.978; respectively) and low-density lipoprotein (LDL) cholesterol (128±22 versus 120±25 mg/dL, p=0.042 and 120±23 versus 121±22 mg/dL, p=0.622; respectively). Noteworthy is that both treatments significantly reduced epinephrine-induced platelet aggregation (78.9±16% versus 71.7±23%, p=0.013 and 81.3±15% versus 73.3±23%, p=0.036; respectively). Thus, oral magnesium oxide treatment significantly improved [Mg2+]i, total and LDL cholesterol compared with magnesium citrate, while both treatments similarly inhibited platelet aggregation in healthy subjects with no apparent heart disease.
The incidence of insulin resistance and metabolic syndrome correlates with the availability of magnesium (Mg). We studied the effect of oral Mg supplementation on insulin sensitivity and other characteristics of the metabolic syndrome in normomagnesemic, overweight, insulin resistant, non-diabetic subjects. Subjects were tested for eligibility using oral glucose tolerance test (OGTT) and subsequently randomized to receive either Mg-aspartate-hydrochloride (n = 27) or placebo (n = 25) for 6 months. As trial endpoints, several indices of insulin sensitivity, plasma glucose, serum insulin, blood pressure and lipid profile were determined. Mg supplementation resulted in a significant improvement of fasting plasma glucose and some insulin sensitivity indices (ISIs) compared to placebo. Blood pressure and lipid profile did not show significant changes. The results provide significant evidence that oral Mg supplementation improves insulin sensitivity even in normomagnesemic, overweight, non-diabetic subjects emphasizing the need for an early optimization of Mg status to prevent insulin resistance and subsequently type 2 diabetes.
A large number of mammalian Mg(2+) transporters have been hypothesized on the basis of physiological data, but few have been investigated at the molecular level. The recent identification of a number of novel proteins that mediate Mg(2+) transport has enhanced our understanding of how Mg(2+) is translocated across mammalian membranes. Some of these transporters have some similarity to those found in prokaryocytes and yeast cells. Human Mrs2, a mitochondrial Mg(2+) channel, shares many of the properties of the bacterial CorA and yeast Alr1 proteins. The SLC41 family of mammalian Mg(2+) transporters has a similarity with some regions of the bacterial MgtE transporters. The mammalian ancient conserved domain protein (ACDP) Mg(2+) transporters are found in prokaryotes, suggesting an ancient origin. However, other newly identified mammalian transporters, including TRPM6/7, MagT, NIPA, MMgT, and HIP14 families, are not represented in prokaryotic genomes, suggesting more recent development. MagT, NIPA, MMgT, and HIP14 transporters were identified by differential gene expression using microarray analysis. These proteins, which are found in many different tissues and subcellular organelles, demonstrate a diversity of structural properties and biophysical functions. The mammalian Mg(2+) transporters have no obvious amino acid similarities, indicating that there are many ways to transport Mg(2+) across membranes. Most of these proteins transport a number of divalent cations across membranes. Only MagT1 and NIPA2 are selective for Mg(2+). Many of the identified mammalian Mg(2+) transporters are associated with a number of congenital disorders encompassing a wide range of tissues, including intestine, kidney, brain, nervous system, and skin. It is anticipated that future research will identify other novel Mg(2+) transporters and reveal other diseases.
This study compared magnesium oxide and magnesium citrate with respect to in vitro solubility and in vivo gastrointestinal absorbability. The solubility of 25 mmol magnesium citrate and magnesium oxide was examined in vitro in solutions containing varying amounts of hydrochloric acid (0-24.2 mEq) in 300 ml distilled water intended to mimic achlorhydric to peak acid secretory states. Magnesium oxide was virtually insoluble in water and only 43% soluble in simulated peak acid secretion (24.2 mEq hydrochloric acid/300 ml). Magnesium citrate had high solubility even in water (55%) and was substantially more soluble than magnesium oxide in all states of acid secretion. Reprecipitation of magnesium citrate and magnesium oxide did not occur when the filtrates from the solubility studies were titrated to pH 6 and 7 to stimulate pancreatic bicarbonate secretion. Approximately 65% of magnesium citrate was complexed as soluble magnesium citrate, whereas magnesium complexation was not present in the magnesium oxide system. Magnesium absorption from the two magnesium salts was measured in vivo in normal volunteers by assessing the rise in urinary magnesium following oral magnesium load. The increment in urinary magnesium following magnesium citrate load (25 mmol) was significantly higher than that obtained from magnesium oxide load (during 4 hours post-load, 0.22 vs 0.006 mg/mg creatinine, p less than 0.05; during second 2 hours post-load, 0.035 vs 0.008 mg/mg creatinine, p less than 0.05). Thus, magnesium citrate was more soluble and bioavailable than magnesium oxide.
Four hundred young normotensive primigravid women between 13 and 24 weeks' gestation were randomly allocated to one of two study groups. One group received placebo tablets and the other group received 365 mg of elemental magnesium daily (as magnesium aspartate hydrochloride). Three hundred seventy-four patients completed the study, 189 in the placebo group and 185 in the treatment group. There were no significant differences between the two groups regarding serum calcium, uric acid, or electrolyte levels. However, the magnesium-supplemented group had significantly higher magnesium levels at delivery (1.68 +/- 0.03 mg/dl vs. 1.56 +/- 0.03 mg/dl, p less than 0.01). There were no significant differences in either systolic or diastolic blood pressures between both groups either at time of enrollment or at subsequent gestational ages later during pregnancy. Analysis of variance for repeated measurements and Fisher's least significant difference testing indicated a significant increase (p less than 0.01) in blood pressure from the level at the time of enrollment to the level achieved at or beyond 37 weeks' gestation in each group. There were no significant differences between the two groups regarding any of the following parameters: incidences of preeclampsia, fetal growth retardation, preterm labor, birth weight, gestational age at delivery, or number of infants admitted to the special care unit. Magnesium supplementation during pregnancy did not improve pregnancy outcome in our population.
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.
Magnesium plasma concentrations were measured in healthy probands before and after administration of trimagnesium dicitrate by the oral and intravenous routes. There was a notable circadian fluctuation of the plasma concentration with a peak in the evening hours. After oral administration of 12 and 24 mmol magnesium, a long-lasting, statistically significant increase in plasma magnesium concentration measured as the increase in area under the curve (AUC) between 0 and 12 h, of 3.1% and 4.6%, respectively, was found. After intravenous administration of 4 and 8 mmol magnesium, AUCs increased by 9.5% and 16.1%, respectively. The decline in the plasma magnesium concentration after i.v. administration was compatible with a three-compartment model with a terminal half-time of about 8 h. Although no absolute value of the oral bioavailability of trimagnesium dicitrate could be determined from the data, our results may be important in helping to elucidate the influence of magnesium preparations on the plasma magnesium concentration. By comparing the effects of different preparations, it should be possible to estimate the relative oral bioavailability and the bioequivalence of these preparations.
Based on a recently proposed reference range for plasma/serum Mg with its lower limit set at 0.76 mmol Mg/L the frequency of hypomagnesemia was evaluated in an unselected population group of about 16,000 individuals in total as well as in subgroups built according to sex, age and state of health. Hypomagnesemia was present in about 14.5 percent of all persons with generally higher frequencies in females and outpatients. In addition a slight but significant effect of age became overt. There was a continuous increase in the frequency of hypomagnesemia until the 29th year of life followed by a steady state. In elderlies, especially in old ladies, highest prevalence of up to one third of this subgroup occurred. Suboptimal levels were detected in 33.7 per cent of the population under study. These data clearly demonstrate that the Mg supply of the German population needs increased attention.
Published data on the bioavailability of various Mg preparations is too fragmented and scanty to inform proper choice of Mg preparation for clinical studies. In this study, the relative bioavailability of three preparations of Mg (amino-acid chelate, citrate and oxide) were compared at a daily dose of 300 mg of elemental Mg in 46 healthy individuals. The study was a randomised, double-blind, placebo-controlled, parallel intervention, of 60 days duration. Urine, blood and saliva samples were taken at baseline, 24 h after the first Mg supplement was taken ('acute' supplementation) and after 60 days of daily Mg consumption ('chronic' supplementation). Results showed that supplementation of the organic forms of Mg (citrate and amino-acid chelate) showed greater absorption (P = 0.033) at 60 days than MgO, as assessed by the 24-h urinary Mg excretion. Mg citrate led to the greatest mean serum Mg concentration compared with other treatments following both acute (P = 0.026) and chronic (P = 0.006) supplementation. Furthermore, although mean erythrocyte Mg concentration showed no differences among groups, chronic Mg citrate supplementation resulted in the greatest (P = 0.027) mean salivary Mg concentration compared with all other treatments. Mg oxide supplementation resulted in no differences compared to placebo. We conclude that a daily supplementation with Mg citrate shows superior bioavailability after 60 days of treatment when compared with other treatments studied.
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