Yoon Hang Kim, MD, MPH

Abstract

Magnesium is an essential mineral required for hundreds of enzymatic reactions, yet nearly half of U.S. adults fail to meet recommended dietary allowances. While various magnesium supplements are available, they differ significantly in bioavailability, gastrointestinal tolerance, and evidence for specific clinical indications. This review examines five common supplemental forms—citrate, glycinate, L-threonate, malate, and oxide—analyzing their relative absorption, therapeutic applications, benefits, and limitations. Understanding these differences enables clinicians and patients to select the most appropriate form based on individual needs, whether for constipation relief, sleep support, cognitive enhancement, musculoskeletal health, or general magnesium repletion.

Introduction

Magnesium serves as a cofactor in over 300 enzymatic reactions essential for energy production, neuromuscular function, glucose metabolism, and cardiovascular health. Despite its critical importance, magnesium deficiency remains prevalent, with inadequate intake linked to hypertension, cardiac arrhythmias, migraine headaches, and metabolic dysregulation (UCLA Health, 2025). While healthy kidneys excrete excess dietary magnesium, supplemental forms require careful selection due to variations in absorption, tolerability, and clinical efficacy.

This review synthesizes current evidence on five commonly used magnesium supplements, providing practical guidance for integrative medicine practitioners and informed patients seeking to optimize their magnesium status.

Comparative Overview of Magnesium Forms

Table 1 summarizes the key characteristics of each magnesium form, including absorption profiles, primary clinical uses, and safety considerations.

Table 1. Comparative characteristics of common magnesium supplement forms.

Detailed Analysis by Magnesium Form

Magnesium Citrate

Magnesium citrate demonstrates relatively high oral bioavailability compared with inorganic salts, making it effective for correcting magnesium deficiency (Professional Supplement Center, n.d.). Its dual action as both a systemic magnesium source and osmotic laxative makes it particularly valuable for patients with concurrent deficiency and constipation. The compound works by drawing water into the intestinal lumen, typically producing bowel movements within 30 minutes to 6 hours of administration (Cleveland Clinic, n.d.).

However, this laxative effect represents both a benefit and a limitation. Common adverse effects include abdominal cramping, gas, nausea, and diarrhea, particularly with higher doses (Medical News Today, n.d.). More concerning, excessive use or administration in patients with renal impairment can cause dangerous electrolyte disturbances, including hypermagnesemia with associated hypotension and cardiac complications. Patients on sodium-restricted diets or taking interacting medications such as fluoroquinolone antibiotics or bisphosphonates should avoid magnesium citrate or use it only under medical supervision (MedlinePlus, n.d.).

Magnesium Glycinate

Magnesium glycinate chelates magnesium with the amino acid glycine, enhancing both absorption and gastrointestinal tolerance (Health.com, 2024). This form has gained popularity among integrative practitioners for addressing insomnia, anxiety, muscle cramps, restless leg syndrome, and general magnesium deficiency due to its favorable side effect profile and the potentially calming properties attributed to the glycine component (Banner Health, n.d.).

Despite superior tolerability, magnesium glycinate still carries risks. Doses exceeding 350 mg of elemental magnesium daily increase the likelihood of gastrointestinal disturbances and potential toxicity, especially with chronic use (National Institutes of Health Office of Dietary Supplements, n.d.). Patients with kidney disease, certain cardiac conditions, neuromuscular disorders, or those taking medications such as bisphosphonates or lithium require careful monitoring and may need dose adjustments to prevent hypermagnesemia (National Institutes of Health Office of Dietary Supplements, n.d.).

Magnesium L-Threonate

Magnesium L-threonate represents a novel approach to magnesium supplementation, specifically engineered to enhance brain magnesium levels. Animal studies demonstrate that this form uniquely elevates cerebrospinal fluid magnesium concentrations, with oral administration increasing brain levels by 7-15% within 24 days—an effect not observed with conventional magnesium compounds (Slutsky et al., 2010). These increased brain levels appear to enhance synaptic density and plasticity through activation of NMDA receptors, potentially explaining observed improvements in learning and memory.

Human evidence, while limited, shows promise. A randomized, double-blind, placebo-controlled trial in adults aged 50-70 years found that magnesium L-threonate supplementation significantly improved overall cognitive scores compared with placebo (p = 0.003; Cohen's d = 0.91), with particularly notable benefits in memory domains (Liu et al., 2016). A subsequent study in healthy Chinese adults aged 18-65 years confirmed these findings, demonstrating significant improvements across all five subcategories of the Clinical Memory Test as well as overall memory quotient scores after 30 days of supplementation (Zhang et al., 2022).

Despite encouraging results, several limitations warrant consideration. The human evidence base remains relatively small, with only a handful of published trials. Additionally, magnesium L-threonate contains less elemental magnesium per dose than other forms and costs significantly more, making it impractical as a primary source for whole-body magnesium repletion. The standard magnesium toxicity concerns, particularly in patients with renal impairment, still apply (National Institutes of Health Office of Dietary Supplements, n.d.).

Magnesium Malate

Magnesium malate combines magnesium with malic acid, a Krebs cycle intermediate involved in cellular energy production. This form demonstrates good absorption and has gained clinical use for musculoskeletal complaints, particularly fibromyalgia and chronic fatigue syndrome (Tua Saúde, n.d.). The theoretical rationale centers on malic acid's role in ATP synthesis, suggesting potential synergy for addressing energy-related symptoms.

Clinical evidence for magnesium malate in fibromyalgia and chronic pain remains mixed and limited compared with more established magnesium forms. While some literature and clinical experience suggest benefits for reducing chronic pain and fatigue, particularly in conditions where magnesium deficiency contributes to symptoms, robust controlled trials are lacking (Dr. Axe, n.d.). Common adverse effects at higher doses include nausea, vomiting, diarrhea, abdominal pain, and gas (Tua Saúde, n.d.). Magnesium malate appears most appropriate as an adjunct therapy rather than standalone treatment for these conditions.

Magnesium Oxide

Magnesium oxide presents a paradox in supplementation: despite containing a high percentage of elemental magnesium by weight, it demonstrates remarkably poor bioavailability, with absorption studies showing rates as low as 0-4% (Healthline, n.d.). The bulk of an oral dose remains in the gastrointestinal lumen, where it exerts osmotic effects useful for constipation relief and acid neutralization.

The low cost and widespread availability of magnesium oxide make it attractive for certain applications, particularly as a laxative or antacid. However, the same properties that enable these effects—high concentration in the gut lumen—frequently cause diarrhea, bloating, and cramping, especially at higher doses (Healthline, n.d.). More concerning, chronic high-dose use (exceeding 1,000 mg daily) or administration in patients with kidney disease can still lead to hypermagnesemia, manifesting as hypotension, cardiac arrhythmias, respiratory depression, confusion, and in severe cases, coma or death (Dr. Axe, n.d.). For systemic magnesium repletion, better-absorbed forms represent superior choices.

Universal Magnesium Supplementation Considerations

Regardless of form, all magnesium supplements share certain characteristics and precautions. The mineral plays essential roles in energy metabolism, nerve function, muscle contraction, and vascular tone. Deficiency has been linked to numerous conditions including hypertension, arrhythmias, migraine, and metabolic disorders, justifying supplementation in appropriate clinical contexts (Medical News Today, n.d.).

However, supplementation carries inherent risks distinct from dietary magnesium. While healthy kidneys readily excrete excess magnesium from food sources, supplemental forms can overwhelm this regulatory mechanism. Diarrhea represents the most common adverse effect across all forms, though threshold doses vary. More serious hypermagnesemia, characterized by hypotension, bradycardia, and central nervous system depression, becomes a concern with renal impairment, advanced age, or high-dose chronic supplementation (Medical News Today, n.d.).

Drug interactions warrant attention across all magnesium forms. The mineral can chelate with certain antibiotics (particularly fluoroquinolones and tetracyclines), reducing both magnesium and antibiotic absorption. Similar interactions occur with bisphosphonates used for osteoporosis. Separation of doses by at least 2-4 hours generally prevents these interactions (Medical News Today, n.d.). Additionally, magnesium can potentiate the effects of certain antihypertensive medications and muscle relaxants, necessitating monitoring when used concurrently.

Clinical Selection Framework

Selection of magnesium form should follow a systematic approach based on therapeutic goals, patient tolerance, and individual risk factors:

For general systemic magnesium repletion, magnesium glycinate or citrate typically serve as first-line options due to superior bioavailability and tolerability. Glycinate offers advantages for patients prone to gastrointestinal sensitivity, while citrate benefits those with concurrent constipation (UCLA Health, 2025).

For cognitive support, particularly in middle-aged and older adults, magnesium L-threonate demonstrates the strongest form-specific evidence, though cost considerations and the need for adequate whole-body magnesium may necessitate combination with a more economical form (Zhang et al., 2022). The evidence base, while promising, remains emerging and should be positioned as adjunctive rather than disease-modifying therapy.

For constipation or bowel preparation, magnesium citrate or oxide provide reliable osmotic effects. However, both require careful attention to renal function and hydration status to minimize risks of electrolyte disturbances (Cleveland Clinic, n.d.).

For musculoskeletal complaints, particularly fibromyalgia or chronic fatigue, magnesium malate may offer theoretical advantages through its role in cellular energy production, though evidence remains limited and the form is best employed as part of a comprehensive treatment approach (Tua Saúde, n.d.).

Conclusion

The diverse array of magnesium supplements reflects genuine biochemical and clinical differences rather than mere marketing distinctions. Magnesium citrate and glycinate offer reliable systemic absorption with distinct gastrointestinal profiles. Magnesium L-threonate provides unique benefits for cognitive function through enhanced brain bioavailability, while malate shows promise for energy-related musculoskeletal complaints. Magnesium oxide, despite poor absorption, serves specific roles as an economical laxative and antacid. Understanding these differences, combined with individual patient factors and therapeutic goals, enables rational selection that optimizes both efficacy and safety. As with all supplementation, a food-first approach should be encouraged when feasible, with supplements reserved for documented deficiency, specific clinical indications, or when dietary sources prove inadequate.

References

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