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Magnesium citrate
Magnesium citrate
Magnesium citrate
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Magnesium citrate
Names
IUPAC name
Magnesium 2-hydroxypropane-1,2,3-tricarboxylate
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.121.319 Edit this at Wikidata
EC Number
  • 231-923-9
E number E345 (antioxidants, ...)
UNII
  • 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 checkY
    Key: PLSARIKBYIPYPF-UHFFFAOYSA-H checkY
  • C(C(=O)O)C(CC(=O)[O-])(C(=O)[O-])O.[Mg+2]
Properties
C6H6MgO7
Molar mass 214.412 g·mol−1
20 g/100ml
Pharmacology
A06AD19 (WHO) A12CC04 (WHO), B05CB03 (WHO)
Related compounds
Related salts
 Magnesium citrate (3:2)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Magnesium citrates are metal-organic compounds formed from citrate and magnesium ions. They are salts. One form is the 1:1 magnesium preparation in salt form with citric acid in a 1:1 ratio (1 magnesium atom per citrate molecule). It contains 11.33% magnesium by weight. Magnesium citrate (sensu lato) is used medicinally as a saline laxative and to empty the bowel before major surgery or a colonoscopy. It is available without a prescription, both as a generic and under various brand names. It is also used in the pill form as a magnesium dietary supplement. As a food additive, magnesium citrate is used to regulate acidity and is known as E number E345.

Structures

[edit]

The structures of solid magnesium citrates have been characterized by X-ray crystallography. In the 1:1 salt, only one carboxylate of citrate is deprotonated. It has the formula Mg(H2C6H5O7)2 The other form of magnesium citrate has the formula Mg(HC6H5O7)(H2O)2, consisting of the citrate dianion (both carboxylic acids are deprotonated).[1] Thus, it is clear that name "magnesium citrate" is ambiguous and sometimes may refer to other salts such as trimagnesium dicitrate which has a magnesium:citrate ratio of 3:2, or monomagnesium dicitrate with a ratio of 1:2, or a mix of two or three of the salts of magnesium and citric acid.

Mechanism of action

[edit]

Magnesium citrate works by attracting water through the tissues by a process known as osmosis. Once in the intestine, it can attract enough water into the intestine to induce defecation.[2][3] The additional water stimulates bowel motility. This means it can also be used to treat rectal and colon problems. Magnesium citrate functions best on an empty stomach, and should always be followed with a full (eight-ounce or 250 ml) glass of water or juice to help counteract water loss and aid in absorption. Magnesium citrate solutions generally produce bowel movement in one-half to three hours.[4]

Use and dosage

[edit]

The maximum upper tolerance limit (UTL) for magnesium in supplement form for adults is 350 mg of elemental magnesium per day, according to the National Institutes of Health (NIH) In addition, according to the NIH, total dietary requirements for magnesium from all sources (in other words, food and supplements) is 320–420 mg of elemental magnesium per day, though there is no UTL for dietary magnesium.[5]

Laxative

[edit]

Magnesium citrate is used as a laxative agent.[6]

Magnesium deficiency treatment

[edit]

Although less common, as a magnesium supplement the citrate form is sometimes used because it is believed to be more bioavailable than other common pill forms, such as magnesium oxide.[7] But, according to one study, magnesium gluconate was found to be marginally more bioavailable than even magnesium citrate.[8]

Potassium-magnesium citrate, as a supplement in pill form, is useful for the prevention of kidney stones.[9]

Side effects

[edit]

Magnesium citrate is generally not a harmful substance, but care should be taken by consulting a healthcare professional if any adverse health problems are suspected or experienced. Extreme magnesium overdose can result in serious complications such as slow heartbeat, low blood pressure, nausea, drowsiness, etc. If severe enough, an overdose can even result in coma or death.[10][11] However, a moderate overdose will be excreted through the kidneys, unless one has serious kidney problems. Rectal bleeding or failure to have a bowel movement after use could be signs of a serious condition.

See also

[edit]

References

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Magnesium citrate

View on Grokipedia
from Grokipedia
Magnesium citrate, also known as trimagnesium dicitrate, is an with the C₁₂H₁₀Mg₃O₁₄ and a molecular weight of 451.12 g/mol, consisting of magnesium cations bound to citrate anions in a 3:2 ratio. It appears as a white, hygroscopic powder that is partially soluble in cold water and has a of approximately 184°C. This compound is primarily utilized as a saline laxative for short-term relief of occasional and to facilitate bowel evacuation prior to diagnostic procedures like , working by drawing water into the intestines to soften stool and stimulate , with effects typically onsetting within 30 minutes to 6 hours. Magnesium citrate is available over-the-counter in forms such as oral solutions or powders mixed with water and is approved by the FDA as an in osmotic products. It is not intended for prolonged use beyond one week without medical supervision due to risks of . Beyond its role, magnesium citrate functions as a to address , providing a highly bioavailable source of this essential that supports over 300 enzymatic reactions, including those for muscle and function, energy metabolism, protein synthesis, and regulation. The recommended dietary allowance for magnesium varies by age and sex, but supplements like magnesium citrate are often taken in doses up to 350 mg elemental magnesium daily for adults to maintain optimal health. Common side effects include loose or watery stools, abdominal cramping, and , which are generally mild but can indicate overuse; severe reactions such as or persistent warrant immediate medical attention. Precautions are advised for individuals with impairment, as reduced excretion may lead to magnesium accumulation, and it should be taken separately from other medications to avoid interactions. Additionally, magnesium citrate is employed in food additives, , and pharmaceutical formulations as an acidity regulator and stabilizer.

Chemistry

Chemical structure

Magnesium citrate encompasses a family of ionic salts derived from the reaction of magnesium cations (Mg²⁺) with (C₆H₈O₇), featuring varying states and stoichiometric ratios that influence their chemical properties. The primary variants include the dibasic form, known as magnesium hydrogen citrate, with a 1:1 magnesium-to-citrate ratio and the molecular formula Mg(HC₆H₅O₇), and the tribasic form, trimagnesium dicitrate, with a 3:2 ratio and formula Mg₃(C₆H₅O₇)₂. These structures arise from the trivalent citrate anion (C₆H₅O₇³⁻) coordinating with Mg²⁺, often accompanied by molecules in hydrated forms such as Mg(HC₆H₅O₇)·2H₂O for the dibasic variant or Mg₃(C₆H₅O₇)₂·9H₂O for the tribasic. The magnesium content by weight varies depending on the variant and hydration state, typically ranging from approximately 11.33% in the anhydrous dibasic form (molecular weight 214.41 g/mol, with Mg at 24.31 g/mol) to 16.2% in the anhydrous tribasic form (molecular weight 451.11 g/mol). Hydrated forms, such as the nonahydrate of trimagnesium dicitrate, lower this to around 11.9% due to the added mass of molecules. X-ray crystallography reveals that Mg²⁺ in magnesium citrate adopts an octahedral (MgO₆), with oxygen ligands from carboxylate groups, hydroxyl groups of the citrate, and molecules. In the dibasic citrate dihydrate Mg(HC₆H₅O₇)(H₂O)₂, the citrate adopts a trans, trans conformation and tridentately chelates Mg²⁺ through a terminal oxygen (O14), central oxygen (O15), and hydroxyl oxygen (O17), supplemented by two molecules, with Mg–O distances between 2.000 Å and 2.089 Å and isolated octahedra. The citrate ion thus acts as a multidentate , with the Mg²⁺ center showing distorted octahedral symmetry due to the asymmetric binding of the propionate chain in . The chemical formulas can be represented as follows: For dibasic magnesium citrate:
\ceMg(HC6H5O7)\ce{Mg(HC6H5O7)} For trimagnesium dicitrate:
\ceMg3(C6H5O7)2\ce{Mg3(C6H5O7)2} Schematic diagrams of citrate binding typically depict the citrate's central carbon bearing the hydroxyl group and three carboxylate arms, with Mg²⁺ bridged or chelated by two or three oxygen atoms from these functional groups, often visualized in crystal packing as hydrogen-bonded networks involving water.

Physical and chemical properties

Magnesium citrate appears as a or off-white, odorless powder or crystalline solid, commonly encountered in hydrated forms such as the nonahydrate or tetrahydrate. It exhibits high in , approximately 20 g/100 mL at 20°C, rendering it suitable for aqueous formulations, while it is slightly soluble in alcohol and insoluble in . Aqueous solutions of magnesium citrate typically have a in the range of 5.0 to 9.0, depending on concentration and form, though they tend to be acidic (around 4.0 at higher concentrations) due to residual components. Magnesium citrate is hygroscopic and sensitive to moisture, necessitating dry storage conditions to prevent clumping, though it remains stable under normal temperatures and pressures; occurs above 200°C, yielding magnesium oxides and carbon oxides. In aqueous solutions, magnesium citrate readily releases magnesium ions due to its high (up to 55% in neutral water), which contributes to its superior compared to less soluble forms like , as evidenced by greater urinary excretion and serum levels in human studies.

Synthesis and production

Magnesium citrate is primarily synthesized through an acid-base neutralization reaction between a magnesium source, such as or magnesium carbonate, and in an aqueous medium, followed by , , and to isolate the product. In this process, is first dissolved in and heated to approximately 70°C, after which the magnesium precursor is gradually added while maintaining a range of 5–8 to ensure complete reaction and minimize impurities like lead; the mixture is then cooled to promote , washed with hot deionized , dried at 70–80°C, and optionally further dehydrated at 150°C for the form. The reaction with , for instance, proceeds as follows: 3MgO+2C6H8O7→Mg3(C6H5O7)2+3H2O3 \text{MgO} + 2 \text{C}_6\text{H}_8\text{O}_7 \rightarrow \text{Mg}_3(\text{C}_6\text{H}_5\text{O}_7)_2 + 3 \text{H}_2\text{O} This yields water as the primary byproduct, contributing to an environmentally friendly process with minimal waste generation. An alternative synthesis route employs magnesium hydroxide as the precursor, reacted with citric acid under controlled pH (5–8) and temperature (up to 90°C) conditions to form the citrate salt, which is then separated via solid-liquid filtration once precipitation exceeds 50% and processed similarly through drying and sieving. Another variant starts from natural dolomite, which is calcined at 1000°C, converted to basic magnesium carbonate via sulfuric acid treatment, and then combined with citric acid in distilled water, followed by ethanol precipitation and room-temperature drying to yield the nonahydrate form with approximately 70% efficiency in laboratory settings. On a commercial scale, magnesium citrate is manufactured as a (E345) for acidity regulation or in pharmaceutical-grade forms compliant with (USP) standards, involving additional purification steps such as acetic acid addition for heavy metal control and with for enhanced handling. These processes achieve purities exceeding 99%, with scalability supported by the use of high-purity magnesium sources like (providing 60% magnesium content) for faster reaction kinetics and cost-effectiveness compared to alternatives like or carbonate. Energy inputs primarily involve heating for dissolution and reaction (70–90°C) and extended (up to 60 hours at 150°C for product), while focuses on and solvents to maintain low environmental impact.

Pharmacology

Mechanism of action

Magnesium citrate functions primarily as an osmotic in the . Upon ingestion, it dissociates into magnesium ions (Mg²⁺) and citrate ions in the acidic environment of the and . The poorly absorbed Mg²⁺ ions remain in the intestinal lumen, creating a hyperosmotic that draws from surrounding tissues into the bowel via . This influx of increases the volume and liquidity of the stool, distends the intestinal walls, and stimulates , thereby promoting . Additionally, the citrate ions contribute to this effect by further enhancing the osmotic pull and may stimulate the release of cholecystokinin, a hormone that augments intestinal motility. The osmotic mechanism is particularly pronounced in the colon, where unabsorbed magnesium ions establish a sustained , leading to rapid retention and fecal evacuation. The onset of action typically occurs within 0.5 to 3 hours, attributable to the compound's rapid and in the gut lumen, which allows quick establishment of the osmotic effect. The citrate component specifically improves magnesium's in aqueous environments, facilitating its dissociation and overall efficacy as a agent compared to less soluble magnesium salts. As a magnesium supplement, magnesium citrate ionizes in the digestive tract to release bioavailable Mg²⁺ ions, which are absorbed primarily in the through paracellular passive diffusion and transcellular involving TRPM6/7 channels. Once absorbed, Mg²⁺ binds to proteins and serves as a cofactor for over 300 enzymes, playing a pivotal role in cellular energy metabolism by stabilizing (ATP) in its Mg-ATP complex, which is essential for and energy transfer during biochemical reactions. Mg²⁺ also supports function by modulating channels and release, helping to maintain neuronal excitability and . In muscle , it promotes relaxation by acting as a natural antagonist, counteracting Ca²⁺ influx that triggers contraction and thereby preventing excessive muscle tension. The citrate moiety enhances the supplement's absorption efficiency, with studies showing higher of magnesium from citrate forms due to improved and gastrointestinal uptake.

Pharmacokinetics

Magnesium citrate is primarily absorbed in the , where the citrate component enhances and compared to less soluble forms like . The chelating effect of citrate facilitates magnesium ion (Mg²⁺) uptake through paracellular pathways and possibly transcellular transporters such as TRPM6. Studies indicate that organic magnesium salts, including citrate, exhibit absorption rates of approximately 50% to 67%, higher than inorganic forms due to improved gastrointestinal across varying conditions. Following absorption, Mg²⁺ is distributed predominantly intracellularly, with 50% to 60% stored in and the remainder in soft tissues, including muscles and organs. Only about 1% circulates in plasma, where levels typically peak 1 to 4 hours after , reflecting rapid uptake and equilibration. This distribution supports magnesium's roles in enzymatic reactions and cellular functions, with serving as a reservoir for long-term . Magnesium itself is not metabolized in the body but functions as a cofactor in numerous biochemical processes; the citrate moiety, however, is metabolized through the Krebs cycle to produce energy. Homeostatic regulation of magnesium occurs primarily via renal mechanisms, with (PTH) modulating reabsorption in the to maintain serum levels. Excretion of magnesium occurs mainly through the kidneys, accounting for about 95% of absorbed magnesium via , while unabsorbed portions are eliminated in . The kidneys filter approximately 2,400 mg daily but reabsorb about 70-90% in the and thick ascending limb, with fine-tuning in the to achieve overall 95-99% reabsorption. The plasma half-life of magnesium is approximately 8 to 9 hours, though total body extends to around 1,000 hours due to bone storage. Pharmacokinetics of magnesium citrate are influenced by several factors, including vitamin D, which enhances intestinal absorption by upregulating transport proteins; PTH, which primarily affects renal reabsorption; and gastrointestinal pH, where acidic conditions improve citrate solubility and thus magnesium uptake. These elements collectively determine net bioavailability and steady-state levels.

Medical uses

As a laxative

Magnesium citrate serves as a primary treatment for short-term relief of occasional and is classified as a saline osmotic . Among various forms of magnesium supplements, magnesium citrate is often considered the most effective for constipation relief due to its strong osmotic laxative properties. As an osmotic laxative, it draws water into the intestines, softening stool and promoting bowel movements, often resulting in loose, watery stools or diarrhea as a common side effect, typically producing results within 30 minutes to 6 hours after ingestion. Clinical evidence supports its high efficacy, with studies reporting success rates of 85-98% for achieving adequate bowel evacuation or cleansing, particularly in the context of preparation for procedures like . It is often preferred for such applications due to its rapid onset and reliable purgative effects compared to bulk-forming or . Systematic reviews of over-the-counter therapies, including two high-quality placebo-controlled trials on magnesium-containing agents, demonstrate significant improvements in bowel movement frequency and stool consistency, establishing its role in acute relief. The medication is commonly available as an oral solution, such as the brand Citroma, which is frequently lemon-flavored to enhance tolerability, though chilling may further improve taste. Guidelines emphasize its use only for occasional , not chronic conditions, to avoid dependency or imbalances. Meta-analyses, particularly those evaluating osmotic preparations for bowel cleansing, indicate magnesium citrate provides comparable efficacy to alternatives like in adults, with adequate preparation rates exceeding 90% in multiple randomized trials. In special populations, such as , magnesium citrate is used with age-adjusted dosing—typically 2-6 mL/kg per day for disimpaction or cleansing under medical supervision—to ensure safety and efficacy while minimizing risks like . For elderly patients, lower starting doses are recommended, with a strong emphasis on adequate hydration to counteract potential from its osmotic effects.

As a magnesium supplement

Magnesium citrate serves as an effective oral supplement for preventing and treating hypomagnesemia, a condition often resulting from poor dietary intake, syndromes, or chronic illnesses such as diabetes mellitus. While effective for supplementation, other forms such as magnesium glycinate may be preferred when avoiding laxative effects due to better absorption and gentler impact on the digestive system. Hypomagnesemia can impair numerous physiological processes, including nerve and muscle function, due to magnesium's role as a cofactor in over 300 enzymatic reactions. The recommended dietary allowance (RDA) for elemental magnesium is 310–320 mg per day for adult women and 400–420 mg per day for adult men, with adjustments for and . Supplementation is particularly indicated when dietary sources, such as leafy greens and nuts, are insufficient to meet these needs. The citrate form is preferred for its superior , which facilitates greater absorption in the compared to inorganic salts like . In a randomized crossover study, magnesium citrate produced a significantly higher rise in serum magnesium levels following both acute and chronic administration than other preparations, with mean serum concentrations peaking at greater levels (P = 0.006 for chronic dosing). This enhanced absorption supports its use in correcting deficiencies more efficiently. Benefits of magnesium citrate supplementation include potential improvements in quality, reduction of muscle , and maintenance of health. For example, magnesium supplementation has been shown to enhance efficiency, total time, and reduce in individuals with primary , as measured by subjective insomnia severity indices. However, while magnesium citrate has good absorption, its laxative effects often make it less ideal for use directly before sleep compared to other forms such as magnesium glycinate, which is better tolerated without gastrointestinal upset and is commonly used for its calming effects on sleep. It may also alleviate muscle , particularly in pregnant individuals, where oral magnesium reduced the frequency and intensity of leg in a randomized trial. Regarding health, supplementation with magnesium citrate at 290 mg per day for postmenopausal women decreased markers of turnover, such as deoxypyridinoline and , while increasing density in multiple randomized controlled trials conducted between 1990 and 2010. A demonstrated the efficacy of magnesium citrate in elevating serum magnesium levels more effectively than other forms. The (NIH) establishes a tolerable upper level of 350 mg per day for supplemental magnesium to minimize risks like gastrointestinal upset, excluding contributions from food sources. Magnesium citrate is commonly available in tablets, capsules, and powders, providing flexible dosing options for daily use. These formulations are frequently combined with calcium or to synergistically support and overall . Monitoring the effectiveness of supplementation involves periodic tests to measure serum magnesium concentrations, with normal levels ranging from 0.75 to 0.95 mmol/L; suboptimal levels may manifest as symptoms including , , and cardiac arrhythmias.

Other uses

Magnesium citrate, often in combination with citrate, is used in the prevention of stones, particularly calcium-based types. It works by increasing urinary citrate levels, which bind to calcium to inhibit crystal formation, and reducing urinary calcium excretion. Clinical guidelines recommend citrate therapy, including formulations with magnesium citrate, for patients with recurrent calcium stones and hypocitraturia, as it significantly lowers recurrence rates compared to . A seminal randomized demonstrated that potassium-magnesium citrate reduced stone recurrence by approximately 85% over three years in patients with idiopathic hypocitraturia. Recent studies from 2020 onward continue to support alkali therapy like potassium-magnesium citrate mixtures, showing up to 79% reduction in new stone formation through modulation of urinary and saturation. Emerging evidence suggests magnesium citrate may support cardiovascular health by aiding regulation and heart rhythm stability. A 2025 systematic review and of randomized controlled trials found that magnesium supplementation, including citrate forms, significantly lowers systolic and diastolic in individuals with and hypomagnesemia, with an average reduction of 2-4 mmHg. In patients with , daily magnesium citrate (400 mg) for 12 weeks decreased both systolic and diastolic pressures. For heart rhythm, short-term magnesium supplementation has been associated with reduced risk of ventricular arrhythmias in patients, attributed to its role in stabilizing cardiac excitability. Magnesium citrate shows potential metabolic benefits, particularly in improving insulin sensitivity and glycemic control among those with . Low serum magnesium levels are linked to , and supplementation may enhance expression and signaling. A 2023 indicated that magnesium intake improves insulin sensitivity markers in at-risk populations, though effects on insulin levels were not always significant. In , higher magnesium consumption correlates with better glucose homeostasis, as evidenced by reduced HOMA-IR scores in observational and interventional studies up to 2025. Beyond medical applications, magnesium citrate serves as a designated E345, primarily to regulate acidity in beverages and processed foods. Approved for use in supplements and fortified products since 2024 in forms like trimagnesium dicitrate, it provides magnesium fortification while acting as a buffering agent without altering flavor significantly. Investigational uses include potential roles in prevention and anxiety management, supported by preliminary data. For , magnesium citrate supplementation (400-600 mg daily) has been shown to reduce attack frequency, duration, and intensity by up to 41.6% in clinical trials, likely due to its effects on neuronal excitability and vascular tone. In anxiety and related mood disorders, 2025 reviews highlight magnesium's involvement in regulation, with early evidence suggesting citrate forms may alleviate symptoms in deficient individuals, though larger trials are needed.

Dosage and administration

For laxative effects

Magnesium citrate is administered orally as a in liquid solution form, typically containing 1.745 g of magnesium citrate per fl oz (providing approximately 290 mg of elemental magnesium per fl oz or 0.98 g per 100 mL). For adults, the recommended dose is 195 to 300 mL taken once daily, not exceeding three consecutive days to minimize risks associated with prolonged use. In pediatric patients, dosing is weight-based and age-adjusted: for children aged 2 to 6 years, 60 to 90 mL once daily; for those aged 6 to 12 years, 90 to 210 mL once daily, with consultation from a healthcare provider essential for precise determination. Administration should occur on an empty , accompanied by a full 8-ounce of water or other clear liquid to enhance efficacy and reduce gastrointestinal discomfort, and it is contraindicated in individuals who are dehydrated due to the potential for exacerbating fluid loss. Use with caution and dose adjustments in patients with renal impairment; avoid in severe cases (e.g., CrCl <30 mL/min) to prevent . Consult healthcare provider for individualized dosing. Use is limited to short-term therapy only, as chronic daily administration can lead to dependency and imbalances.

For supplementation

Magnesium citrate is commonly used as a to address nutritional needs, providing magnesium in a bioavailable form suitable for . For general daily supplementation in adults, recommended doses range from to mg of magnesium per day, typically divided into two to three doses to reduce the risk of gastrointestinal upset such as or . This approach aligns with efforts to maintain adequate magnesium levels without exceeding safe intake thresholds. For therapeutic purposes in cases of (hypomagnesemia), higher doses of up to 600 mg of elemental magnesium per day may be prescribed on a short-term basis, but only under supervision to monitor efficacy and prevent potential adverse effects. Long-term supplementation should not exceed 350 mg of elemental magnesium per day from supplements, as per the (NIH) guidelines, to avoid risks associated with excessive intake. Taking magnesium citrate with meals can enhance absorption and further minimize gastrointestinal discomfort, as food slows transit time and supports uptake in the intestines. Certain populations may require adjusted dosing. Pregnant women are recommended to aim for 350 to 400 mg of elemental magnesium daily to support fetal development and , often through a combination of diet and supplements if dietary intake is insufficient. Athletes, who increased magnesium loss through sweat, may benefit from higher supplementation levels—potentially 10-20% above standard recommendations—tailored to individual needs and activity intensity. Ongoing monitoring is essential for safe supplementation. Periodic laboratory tests, such as serum or magnesium levels, help assess status and guide adjustments, particularly when combined with dietary sources like nuts, seeds, leafy greens, and whole grains that contribute to baseline intake. Supplementation should be personalized based on overall diet, lifestyle, and any underlying conditions to ensure optimal benefits without overcorrection.

Safety and adverse effects

Side effects

Magnesium citrate, when used as a or supplement, commonly causes gastrointestinal side effects due to its osmotic action in the intestines, which draws water into the bowel to promote evacuation. The most frequent adverse reactions include , abdominal cramps, , and vomiting, which are dose-dependent and typically mild to moderate in intensity. These effects occur because magnesium citrate increases intestinal fluid retention, leading to loose stools and peristaltic stimulation, often resulting in diarrhea or loose stools within 30 minutes to 6 hours after ingestion. Other common gastrointestinal complaints are and , often accompanying the primary response. In applications, has an incidence exceeding 10%, as it is the intended therapeutic outcome, though excessive looseness can cause discomfort. Combining magnesium citrate with other laxatives (such as stimulant or additional osmotic types) can amplify these effects, increasing the risk of severe diarrhea, dehydration, abdominal cramping, and electrolyte imbalances (such as changes in sodium, potassium, and calcium levels), as well as potential hypermagnesemia, particularly with overuse, long-term use, or in individuals with kidney or heart conditions. It is not recommended to combine laxatives without medical supervision due to the potential for disrupting body electrolyte balance and causing dependency. For supplementation at lower doses, such as 200-400 mg daily, gastrointestinal side effects like mild are possible but vary by individual and formulation, while systemic effects like or occur rarely. Rare adverse reactions include allergic responses, manifesting as , itching, or , which require immediate medical attention if severe. These hypersensitivity events are uncommon and not directly tied to the compound's mechanism but may involve excipients in formulations. Management of these side effects involves maintaining adequate hydration to counteract fluid loss from , reducing the dose if symptoms arise during supplementation, and discontinuing use if effects persist or worsen; most resolve spontaneously within 24-48 hours after cessation. As of 2025, no novel severe side effects have been reported in recent updates, though there is heightened clinical awareness of potential electrolyte imbalances, such as , in vulnerable populations like the elderly during prolonged or combined use.

Overdose and toxicity

Overdose of magnesium citrate can lead to , characterized by elevated serum magnesium levels exceeding 5 mmol/L (or approximately 12 mg/dL), which poses a significant due to the compound's high and potential for rapid absorption, particularly when used in high doses as a . Symptoms of severe include , , , respiratory depression, and in extreme cases, or . The primary risk factors for magnesium citrate overdose toxicity include , which impairs magnesium excretion, and advanced age, where reduced renal function heightens vulnerability; animal studies indicate a relatively high acute oral LD50 of greater than 5000 mg/kg in mice, underscoring low inherent toxicity but emphasizing the dangers in susceptible populations. Furthermore, combining magnesium citrate with other laxatives (such as stimulant or additional osmotic types) without medical supervision can amplify its effects, leading to severe diarrhea, dehydration, electrolyte imbalances (e.g., changes in sodium, potassium, and calcium), abdominal cramping, and an increased risk of hypermagnesemia and associated complications, particularly in susceptible individuals such as those with kidney or heart conditions. Treatment for magnesium citrate overdose begins with immediate cessation of intake, followed by supportive measures such as intravenous fluids to enhance urinary excretion in patients with normal renal function. In severe cases, intravenous serves as the primary to counteract cardiac and neuromuscular effects, while is recommended for individuals with renal failure to rapidly remove excess magnesium. According to 2025 guidelines from poison control centers, enhanced monitoring is advised for elderly patients using magnesium citrate, given their increased overdose risk from and diminished kidney function, with prompt serum magnesium level assessment recommended in suspected cases.

Drug interactions

Magnesium citrate can interfere with the absorption of certain antibiotics, including tetracyclines and quinolones, by forming chelates that reduce their . Similarly, it decreases the absorption of bisphosphonates through complex formation. To mitigate these interactions, administration of magnesium citrate should be separated from these medications by 2 to 4 hours. Concomitant use of magnesium citrate with potassium-sparing diuretics or other magnesium-containing supplements can elevate serum magnesium levels, increasing the risk of , particularly in patients with impaired renal function. Close monitoring of magnesium levels is recommended in such cases. Magnesium citrate reduces the absorption of by , necessitating a minimum 4-hour separation between doses. Long-term use of inhibitors (PPIs) can deplete magnesium stores, potentially leading to hypomagnesemia; supplementation with magnesium citrate may be beneficial but requires regular monitoring. High-fiber meals can decrease magnesium absorption due to binding effects in the . Calcium-rich foods compete with magnesium for uptake in the intestines, further reducing its . As of 2025, emerging evidence highlights interactions with sodium-glucose cotransporter 2 (SGLT2) inhibitors, which can raise serum magnesium levels and thereby heighten the risk of when combined with magnesium citrate; new clinical guidelines recommend monitoring and dose adjustments in diabetic patients on these therapies. There is no established interaction between magnesium citrate and serotonin syndrome, and magnesium supplements are not listed as a risk factor for serotonin syndrome in reliable sources such as Drugs.com. Magnesium citrate does not cause or increase the risk of serotonin syndrome. Magnesium citrate may interact moderately with some selective serotonin reuptake inhibitors (SSRIs) such as sertraline (Zoloft) primarily due to potential electrolyte imbalances resulting from its laxative effects, but this interaction is unrelated to serotonin syndrome. Magnesium supplements are generally considered safe for concomitant use with antidepressants and may provide adjunctive benefits for depression symptoms. Concomitant use of magnesium citrate with other laxatives, such as stimulant laxatives (e.g., bisacodyl or senna) or additional osmotic laxatives, can produce additive effects on bowel evacuation. This may result in severe diarrhea, dehydration, electrolyte imbalances (including alterations in sodium, potassium, and calcium levels), abdominal cramping, and an increased risk of hypermagnesemia, particularly with overuse, long-term administration, or in patients with renal impairment, cardiac conditions, or other predisposing factors. Combining multiple laxatives is generally not recommended without medical supervision, as it may disrupt electrolyte homeostasis and contribute to laxative dependency.

Contraindications

Magnesium citrate is contraindicated in patients with severe renal impairment, defined as a (GFR) less than 30 mL/min, due to the risk of magnesium accumulation in the plasma. It should also be avoided in cases of , , intestinal , or acute surgical abdomen, as these conditions can be exacerbated by the laxative effects leading to potential complications such as perforation or ischemia. Relative contraindications include or myocardial damage, where magnesium can interfere with cardiac conduction, and , as it may worsen neuromuscular weakness by inhibiting release at the . Caution is advised in patients with , since magnesium supplementation can alter calcium balance and potentially aggravate symptoms. Hypersensitivity to magnesium citrate, , or other magnesium salts represents an absolute , with allergic reactions ranging from to reported in rare cases. In pediatric patients, magnesium citrate is not recommended for children under 6 years of age without medical supervision due to risks of or . For frail elderly individuals, use requires close monitoring because of potential declines in renal function that heighten toxicity risks. During pregnancy, magnesium citrate is classified as Category C by the FDA, indicating that have shown adverse effects or there are no adequate human studies, though benefits may outweigh risks; the FDA has transitioned to narrative risk summaries since 2015, and consultation with a healthcare provider is recommended. As of 2025 guidelines, caution is advised in patients with gastrointestinal conditions.

References

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