How Does Magnesium Citrate Compare to Other Forms of Magnesium?
Dr. John Powers, PhD, Microbiology, Partner and Scientific Advisor, Gowling GWL
Despite its essential role in human health, many modern diets are deficient in magnesium. As a result, many consumers select magnesium supplements as a convenient way to meet their daily requirements. Supplements contain a variety of inorganic and organic forms of magnesium, whose effectiveness may depend upon their bioavailability in the body. Magnesium citrate, and other organic magnesium salts, have demonstrated superior bioavailability to inorganic magnesium salts. This makes magnesium citrate an effective source material for oral magnesium supplementation.
Magnesium and Human Health
Role and benefits of magnesium
Magnesium is an essential nutrient for the human body and is known to be involved in more than 300 biochemical reactions affecting key processes such as energy production, bone development, maintaining electrolyte balance, muscle and heart function, as well as protein, DNA, and RNA synthesis.(1,2) Magnesium also plays a role in the transport of sodium and potassium ions across cellular membranes.(3) Recently, magnesium has also been demonstrated to improve bowel movement and frequency thereby reducing functional constipation.(4,5) More than half of the body’s 20-28 g magnesium store is present in bones with the remainder residing in the soft tissues and, to a very minor extent (<1%), in the blood.(6,7)
Dietary magnesium requirements
Adults require approximately 310-420 mg of magnesium daily, and deficiency may lead to irritability, muscle weakness, and irregular heartbeat.(8) Most dietary magnesium typically comes from sources such as fruits, vegetables, leafy greens, and seeds and grains. While magnesium is present in food sources, recent Health Canada findings suggest that many adults have an inadequate dietary intake of magnesium.(9) Due to deficiencies in modern diets, many consumers select magnesium supplements as a convenient way to meet their daily requirements.
Oral magnesium supplements are available in a variety of formats with powders and capsules being the most common. The magnesium contained in these supplements may be from a variety of source materials or forms, generally grouped as follows:
• Inorganic magnesium salts (such as oxides, carbonates, chlorides and hydroxides);
• Organic magnesium salts (such as citrates, lactates, and gluconates); and
• Magnesium complexes or chelates (such as amino acid chelates).
From a formulation or manufacturing perspective, the selection of a specific magnesium source material may be due to a variety of reasons including, but not limited to, cost, solubility and available capsule space. From a biological perspective, it should be noted that source material ultimately affects magnesium absorption and bioavailability.
The absorption of magnesium from oral supplementation occurs primarily in the small intestine with the majority of uptake occurring in the distal jejunum and the ileum.(10,11) Once dissolved in the gastric fluid, magnesium salts dissociate, freeing the ionic magnesium. The majority of the magnesium ions in the intestinal tract are taken up through passive processes mediated by electrochemical gradients and solvent drag, but some uptake occurs via an active transport system. Once absorbed by the intestine, magnesium ions enter the bloodstream for transport to other tissues and organs.
Measuring magnesium absorption
There are two common methods used to estimate absorption/bioavailability of ingested magnesium. The most widely available and practical way to determine intestinal magnesium absorption is by measuring blood serum magnesium levels.(12,13) In serum magnesium analysis, acute changes in the magnesium status of an individual are detected by measuring the concentration of total serum magnesium following magnesium intake. Since serum magnesium does not correlate well with tissue pools of magnesium, this test is considered a poor predictor of intracellular or body magnesium content; however, it remains effective and reliable for measuring rapid extracellular changes in magnesium levels, and to assess intestinal absorption following an oral load of magnesium.(14,15)
Urinary analysis is another common method for assessing magnesium absorption. Once magnesium levels exceed a critical threshold in the kidney, the excess magnesium is excreted in the urine.(16)
In general, the assumption is that the uptake and release of magnesium are in balance;(17) thus, by determining the concentration of magnesium excreted in the urine, one can estimate the amount of magnesium absorbed by the intestine. Drawbacks to this method of analysis are that test subjects must not be magnesium depleted, and timing of the analysis is critical.
Other, less common, proxies for magnesium absorption include measuring an increase in salivary or erythrocyte magnesium concentrations.(18) Stable isotopes of magnesium have also been used to track the absorption of magnesium by the body.(19)
The solubility of minerals in the digestive tract is a major factor driving their uptake.(20) Because much of the absorption of magnesium is via passive transport, the greater the solubility of magnesium salt or complex that is in the gut, the greater the potential for magnesium ion dissociation and subsequent availability for uptake into the intestine. Thus, the solubility of the magnesium supplement factors in its overall bioavailability.
Organic magnesium salts, such as magnesium citrate, are, in general, more soluble than inorganic magnesium salts.(21) The enhanced solubility leads to a greater concentration of magnesium ions in the intestinal tract. Because of this, supplements containing the highly soluble organic salt forms may be more absorbable by the body (and, therefore, more bioavailable) than inorganic salt forms. Indeed, in vitro and clinical studies have demonstrated the superior solubility and bioavailability of oral organic magnesium salts compared to the representative inorganic form, magnesium oxide.(22,23,24) While most studies to date have used urinary magnesium levels as a measure of bioavailability, Wilimzig et al. (1996) further demonstrated that administration of oral magnesium citrate produced a direct increase in plasma magnesium concentrations in healthy volunteers.(25)
Magnesium citrate is regarded as a highly soluble and readily bioavailable form of magnesium.(26) Studies in simulated gastric fluid demonstrate that magnesium citrate remains in solution even as pH increases.(27) This is an important characteristic since the pH of the intestine increases as it progresses distally. The solubility of magnesium citrate in alkaline environments may enhance bioavailability by increasing the availability of free magnesium ions for passive uptake along the intestinal tract. This means that magnesium ions may remain bioavailable further along the intestinal tract, without the need for additional buffers, allowing more opportunity for transport through cellular membranes. Numerous in vitro studies have demonstrated the superior absorption of organic magnesium salts, including magnesium citrate, in comparison with inorganic salts.(28)
Furthermore, magnesium citrate was found to be both more soluble in simulated gastric acid, and more intestinally absorbable than magnesium oxide, as determined by urinary magnesium excretion analysis in healthy volunteers.(29) The results of these parallel in vitro and in vivo tests suggest that magnesium citrate’s increased bioavailability relative to magnesium oxide may be a result of its enhanced solubility in the intestinal tract.
Recently, magnesium in the form of amino acid chelates such as aspartate and bisglycinate (aka diglycinate) have been the focus of advertising campaigns. While these sources have been marketed as being more bioavailable than other common inorganic and organic forms, there is a lack of published data supporting these claims.
On the contrary, Schuette et al. demonstrated that magnesium absorption did not differ between oxide or bisglycinate forms in a group of subjects who had undergone ileal resection.(30) Furthermore, a detailed review of the bioavailability and pharmacokinetics of magnesium from a variety of sources suggest there is little, if any, difference between forms generally regarded as bioavailable (e.g. citrate and glycinate).(31)
In perhaps the best study design to date, the bioavailability of magnesium citrate was found to be superior to both magnesium oxide and a magnesium amino acid chelate. Walker et al. (2003) conducted a parallel intervention study to compare the relative absorbability and bioequivalence of three forms of magnesium (oxide, citrate and amino acid chelate) under acute (24 h) and chronic (60 days) administration of an oral daily dosage.(32)
Subjects were generally healthy and free of conditions or activities known to affect magnesium metabolism and were administered cellulose or sorbitol placebo or 300 mg elemental magnesium per day from one of the following sources: magnesium amino acid chelate, magnesium citrate, magnesium oxide.
Treatment effects were assessed via urinary magnesium excretion, plasma magnesium concentration, erythrocyte magnesium concentration or salivary magnesium concentration.
Chronic supplementation with organic forms of magnesium (magnesium citrate and magnesium amino acid chelate) resulted in a significant increase in urinary magnesium excretion compared to either placebo or magnesium oxide, which is an indirect measure of the increased bioavailability of magnesium citrate.(33)
As further evidence of the increased bioavailability of magnesium citrate both mean plasma and salivary magnesium concentrations were assayed. Only magnesium citrate was found to produce statistically significant increases compared to all other groups following chronic administration.(34)
While this study was designed to determine the differences in magnesium supplementation compared to placebo, it does suggest that supplementation with magnesium citrate may be superior to supplementation with both magnesium oxide and amino acid chelate forms (e.g. bisglycinate, etc.).
Organic magnesium salts, such as magnesium citrate, are highly soluble in the intestinal tract, which leads to high concentrations of ionic magnesium that can be absorbed by the body. In addition, the enhanced bioavailability of magnesium citrate compared with inorganic magnesium salts (oxides, carbonates, chlorides and hydroxides) is well supported. Furthermore, recent investigations have demonstrated magnesium citrate to be equally or even more bioavailable than amino acid chelates like bisglycinates. Therefore, due to its solubility, and its superior bioavailability, magnesium citrate is a highly effective form of magnesium supplementation.
1 World Health Organization, available at: http://www.fao.org/DoCREP/004/Y2809E/y2809e0k.htm
2 Health Canada, available at: http://webprod.hc-sc.gc.ca/nhpid-bdipsn/atReq.do?atid=multi_vitmin_suppl&lang=eng
3 Bara et al. Magnesium Res 1993;6(2):167-177
4 Dupont et al. Clin Gastroenterol Hepatol 2014;12(8):1280-7
5 Bothe et al. Eur J Nutr 2015;Nov.18 ahead of print.
6 Schaafsma. Eur J Clin Nutr 1997;51(1):13-16
7 Benech and Grognet. Magnesium Res 1995;8(3):277-284
8 Mayo Clinic, available at: http://www.mayoclinic.org/drugs-supplements/magnesium-supplement-oral-route-parenteral-route/description/drg-200707309 Health Canada, available at: http://www.hc-sc.gc.ca/fn-an/surveill/nutrition/commun/art-nutr-adult-eng.php
9 Health Canada, available at: http://www.hc-sc.gc.ca/fn-an/surveill/nutrition/commun/art-nutr-adult-eng.php
10 Coudray et al. Magnesium Res 2005;18(4):215-23
11 Ranade and Somberg. Am J Therapeutics 2001;8:345-357
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18 Walker et al. Magnes Res 2003;6(3):183-91
19 Schuette et al. JPEN J Parenter Enteral Nutr 1994;18(5):430-435
20 Coudray et al. Magnesium Research 2005;18(4):215-23
21 Siebrecht, S. OM & Ernährung 2013;144:2-16
22 Lindberg et al. J Amer Col of Nutrition 1990;9(1):48-55
23 Firoz and Graber. Magnesium Research 2001;14(4):257-262
24 Coudray et al. Magnesium Research 2005;18(4):215-23
25 Wilimzig et al. Euro J Clin Pharmacol 1996;49:317-323
26 Ranade and Somberg. Am J Ther 2001;8:345-357
27 Lindberg et al. J Amer Col Nutr 1990;9(1):48-5528
28 Couday et al. Magnesium Res 2005;18(4):215-23
29 Lindberg et al. J Amer Col Nutr 1990;9(1):48-55
30 Schuette et al. J Parenter Enteral Nutr 1994;18:430-435
31 Ranade and Somberg. Am J Ther 2001;8:345-357
32 Walker et al. Magnes Res 2003;6(3):183-91
33 Walker et al. Magnes Res 2003;6(3):183-91
34 Walker et al. Magnes Res 2003;6(3):183-91