Multiple physiological targets including magnesium-dependent enzymes, ion channels, and transporters. Magnesium citrate is a magnesium salt of citric acid that provides bioavailable magnesium when administered orally. Magnesium is an essential mineral that serves as a cofactor for over 300 enzymatic reactions, including those involved in energy metabolism, protein synthesis, and nucleic acid synthesis. It also plays a critical role in muscle and nerve function, blood glucose control, and blood pressure regulation.

Magnesium citrate exhibits its biological activity through the release of magnesium ions, which are essential for numerous physiological functions. As a citrate salt, it also contributes citrate, which can be metabolized in the citric acid cycle. The compound's laxative effect is mediated through osmotic activity in the gastrointestinal tract, drawing water into the bowel and stimulating bowel movements.

In vivo, Magnesium citrate is used as a dietary supplement to maintain adequate magnesium levels in the body. It is also used as a laxative for the treatment of constipation. By providing bioavailable magnesium, it supports various physiological functions including neuromuscular transmission, cardiac function, and bone health. The compound's osmotic laxative effect is mediated through water retention in the intestinal lumen.

In vitro assays for magnesium citrate typically involve measuring the bioavailability and release of magnesium ions. Dissolution studies can be performed to assess the rate of magnesium release from the compound in simulated gastrointestinal fluids. Cellular assays can evaluate the uptake of magnesium by cells and its effects on magnesium-dependent enzymatic activities and cellular functions.

Cellular assays for magnesium citrate involve treating cells with the compound and measuring magnesium uptake and its effects on cellular functions. Readouts include intracellular magnesium levels (measured by fluorescent probes or atomic absorption spectroscopy), effects on magnesium-dependent enzyme activities, and modulation of cellular processes such as muscle contraction, nerve transmission, and energy metabolism.

In vivo studies with magnesium citrate are typically performed in animal models or human subjects to evaluate its bioavailability, efficacy as a magnesium supplement, and laxative effects. The compound is administered orally, and blood magnesium levels, urinary magnesium excretion, and bowel movement frequency are measured as primary endpoints. Magnesium citrate has been widely studied as a dietary supplement and laxative.

Absorption, Distribution and Excretion
It has been reported that after oral administration of magnesium citrate, the average plasma magnesium concentration is approximately 0.7 mmol/L, and the salivary magnesium concentration is approximately 0.28 mmol/L. Magnesium citrate has been reported to have higher absorption and bioavailability compared to other forms of magnesium, such as oral magnesium. Oral administration of magnesium citrate increases urinary magnesium excretion by 40%. Magnesium citrate is also widely excreted in feces because its presence in the intestines relaxes the intestines and draws water in, thereby increasing intestinal motility, and a large portion of the substance is excreted in this way. Biological Half-Life Due to the half-life of available isotopes of magnesium, studying the half-life of magnesium citrate is very difficult.

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Magnesium citrate (Trimagnesium dicitrate) has a molecular formula of C12H10Mg3O14 and a molecular weight of 451.11. It is a white powder that is freely soluble in water. As a dietary supplement and laxative, it is administered orally. The compound is stable under normal storage conditions and should be stored in a cool, dry place.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Currently, there is no clinical information regarding the use of magnesium citrate during lactation. However, other magnesium salts have been studied. Intravenous magnesium sulfate only slightly increases the magnesium concentration in breast milk. Infants have low oral absorption of magnesium, therefore, maternal use of magnesium citrate is not expected to affect serum magnesium levels in breastfed infants. Magnesium citrate supplementation during pregnancy may delay lactation, but it can be taken during lactation without special precautions.
◉ Effects on Breastfed Infants
On the first day postpartum, 50 mothers received either 15 ml of mineral oil or an emulsion of mineral oil with another magnesium salt (magnesium hydroxide), equivalent to 900 mg of magnesium hydroxide, but the specific number of mothers receiving each product was not specified. Additional doses may be given in subsequent days if necessary. No significant abnormal stools were observed in any of the breastfed infants, but all infants were also supplemented with other foods.
◉ Effects on Lactation and Breast Milk
A mother who received intravenous magnesium sulfate for 3 days due to gestational hypertension experienced delayed lactation (stage II) until 10 days postpartum. Although no comprehensive examination was performed, no other specific cause of the delay was identified. A subsequent controlled clinical trial found no evidence of delayed lactation in mothers receiving intravenous magnesium sulfate. Some studies (but not all) have found a trend toward longer first feeding times or shorter suckling times in infants born to mothers who received intravenous magnesium sulfate during delivery, due to placental transfer of magnesium to the fetus.
A study of 40 healthy, vaginally delivered singleton pregnancies compared outcome parameters of women who received continuous oral magnesium aspartate hydrochloride supplementation (mean daily dose 459 mg, range 365–729 mg) for at least 4 weeks prior to delivery with a control group that did not receive magnesium supplementation. In the magnesium-supplemented group, the proportion of women able to exclusively breastfeed their infants at discharge was significantly lower than in the control group (63% vs 80%).

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Protein binding
After magnesium ionization, it will bind highly to plasma proteins, and its binding rate can even account for 90% of the magnesium content in plasma.

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Magnesium citrate is generally recognized as safe (GRAS) when used as a dietary supplement at recommended doses. Common adverse effects include gastrointestinal discomfort, diarrhea, and abdominal cramping, particularly at higher doses. Overdose can lead to hypermagnesemia, which may cause nausea, vomiting, flushing, and in severe cases, cardiac and neurological effects. The compound should be used with caution in patients with renal impairment.

[1]. Magnesium Citrate Increases Pain Threshold and Reduces TLR4 Concentration in the Brain. Biol Trace Elem Res. 2021;199(5):1954-1966.

Magnesium tricitrate is a magnesium salt composed of magnesium ions and citrate ions in a 3:2 ratio. It is a laxative containing citrate (3-). Magnesium citrate is a low-volume osmotic laxative. Its laxative effect is primarily achieved through the high osmotic pressure of the solution, which draws a large amount of fluid to its site of action. The U.S. Food and Drug Administration (FDA) has approved magnesium citrate as an inactive ingredient in approved drug products, with a maximum oral concentration of 237 mg. It is also used as an active ingredient in over-the-counter medications. Magnesium citrate is a citrate salt of magnesium with laxative activity. The laxative effect of magnesium cations appears to stem in part from osmotically mediated water retention, which in turn stimulates intestinal peristalsis. Furthermore, magnesium ions can stimulate the activity of nitric oxide (NO) synthase and increase the biosynthesis of the phospholipid pro-inflammatory mediator platelet-activating factor (PAF) in the intestine. NO can stimulate intestinal secretion through a prostaglandin and cyclic guanosine monophosphate (cGMP)-dependent mechanism, while PAF significantly stimulates colonic secretion and gastrointestinal motility. See also: Magnesium cations (with the active portion)... See more...

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Drug Indications
Magnesium citrate has been used as a bowel preparation agent before colonoscopy, as a laxative. It is also used in over-the-counter products to relieve occasional constipation. Magnesium citrate is also available as a dietary supplement.

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Mechanism of Action
It works primarily through its hyperosmolar properties, which draw large amounts of fluid into the colonic lumen. Additionally, the release of cholecystokinin and activation of muscle peristalsis may also stimulate fluid excretion.

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Pharmacodynamics
It takes effect as early as 30 minutes after administration, with an average onset time of approximately 2 hours and a maximum duration of action of 4 hours. The effects of magnesium citrate are highly dependent on individual hydration status.

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Magnesium citrate (Trimagnesium dicitrate, CAS#: 3344-18-1) is a magnesium salt of citric acid used as a dietary supplement and laxative. It has a molecular formula of C12H10Mg3O14 and a molecular weight of 451.11. The compound provides bioavailable magnesium and supports numerous physiological functions including neuromuscular transmission, cardiac function, and bone health. It is generally recognized as safe for use as a dietary supplement.

C12H10MG3O14

451.11

449.962

3344-18-1

6099959

White to off-white solid powder

309.6ºC at 760 mmHg

155.2ºC

2

14

4

29

211

0

C(C(=O)[O-])C(CC(=O)[O-])(C(=O)[O-])O.C(C(=O)[O-])C(CC(=O)[O-])(C(=O)[O-])O.[Mg+2].[Mg+2].[Mg+2]

PLSARIKBYIPYPF-UHFFFAOYSA-H

InChI=1S/2C6H8O7.3Mg/c2*7-3(8)1-6(13,5(11)12)2-4(9)10;;;/h2*13H,1-2H2,(H,7,8)(H,9,10)(H,11,12);;;/q;;3*+2/p-6

trimagnesium;2-hydroxypropane-1,2,3-tricarboxylate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O: 4.72 mg/mL (10.46 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)