Magnesium is a cofactor in over 300 enzymatic reactions, yet subclinical deficiency affects an estimated 50% of the US population. Dr. Andrea Rosanoff, director of research at the Center for Magnesium Education and Research, notes that serum magnesium testing — the standard clinical measure — misses 60% of deficient patients because only 1% of total body magnesium circulates in blood. A 2021 Nutrients review (68 studies, n=2.2 million participants) found that higher magnesium intake reduced type 2 diabetes risk by 22% and cardiovascular mortality by 18%. The supplement aisle offers a dozen different forms, and they are not interchangeable.
Magnesium oxide contains the highest percentage of elemental magnesium (60%) but has the lowest bioavailability — approximately 4%, according to a 2003 Journal of the American College of Nutrition comparison trial (n=46). A 400 mg oxide tablet delivers roughly 16 mg of absorbed magnesium. It is primarily useful as a laxative and the worst choice for correcting deficiency.
Magnesium citrate is moderately bioavailable (25-30%) and well-studied. It is the standard recommendation for general supplementation and mild constipation. A 2018 trial in Magnesium Research (n=126) found that 300 mg citrate daily for 6 weeks reduced leg cramps by 41% in pregnant women.
Magnesium glycinate has good bioavailability (approximately 45%) and the fewest GI side effects. The glycine carrier may contribute calming effects — glycine itself acts as an inhibitory neurotransmitter. A 2012 Journal of Pharmacological Sciences study found that 3 g of glycine before bed reduced core body temperature by 0.5°C and improved subjective sleep quality. This form is most recommended for sleep support and anxiety.
Magnesium L-threonate was developed specifically for brain penetration. A 2010 study by Dr. Guosong Liu at MIT, published in Neuron, demonstrated it was the only form to significantly increase brain magnesium levels (by 15%) in animal models. A subsequent human trial (n=44 older adults, 12 weeks, 2000 mg daily) showed improvements in executive function equivalent to reversing 9 years of cognitive aging. The evidence is promising but limited to a single research group.
Practical recommendations: for general use, citrate or glycinate at 200-400 mg daily (the RDA is 310-420 mg depending on age and sex). For sleep, glycinate 200-400 mg 30-60 minutes before bed. For cognitive support, threonate 1500-2000 mg daily is reasonable but should be considered unproven until independent replication. Avoid oxide except for laxation. Take with food to reduce GI effects, and space doses 4+ hours from tetracycline antibiotics or bisphosphonates, which magnesium can bind.