Magnesium is the supplement recommendation I give most consistently. Not NMN, not creatine, not the expensive stuff. Magnesium — because the data is quietly overwhelming and most people are deficient. But the form matters more than most people realize.
Why Magnesium Matters
Magnesium is a cofactor in over 300 enzymatic reactions in the human body, involved in ATP synthesis, DNA replication and repair, neuromuscular signaling, blood pressure regulation, glucose metabolism, and sleep initiation (activation of GABA receptors). A 2012 analysis in Nutrition Reviews (Rosanoff et al.) estimated that 48% of Americans consume less than the recommended daily intake from food.
Standard bloodwork doesn't catch it well. Serum magnesium measures only the ~1% of your total body magnesium that circulates in blood. RBC (red blood cell) magnesium testing is more useful but rarely ordered. The clinical downstream effects of marginal deficiency: sleep disruption, muscle cramps, elevated cardiovascular risk, insulin resistance, and anxiety.
The Forms, Explained
Magnesium Oxide — Skip It
Bioavailability: approximately 4% (Firoz & Graber, 2001, Magnesium Research). Oxide is essentially insoluble — it acts primarily as a laxative, not a supplement. You can find it in grocery store vitamins. Pass.
Magnesium Citrate — Useful but Limited
Better bioavailability than oxide (about 30%). Also has a mild laxative effect at higher doses. For sleep or cognitive effects, it's mediocre. Widely available and inexpensive.
Magnesium Glycinate — Best for Sleep and Anxiety
Magnesium bound to glycine. Bioavailability is high (~80% in some estimates). The mechanism that makes glycinate special: glycine itself is an inhibitory neurotransmitter that crosses the blood-brain barrier and activates glycine receptors, producing calming effects independent of the magnesium content.
A 2017 study in Nutrients (Abbasi et al.) found that supplemental magnesium significantly improved insomnia measures in elderly subjects, including sleep onset latency, sleep efficiency, and early morning awakening. GI tolerance is excellent — minimal laxative effect because it's absorbed in the small intestine rather than drawing water into the colon.
Best use cases: Sleep improvement, anxiety and stress, daily general supplementation, muscle cramping and recovery.
Magnesium L-Threonate — For the Brain
Magnesium L-threonate (MgT) was specifically developed to maximize brain magnesium levels. Created by Guosong Liu and colleagues at MIT; their 2010 paper in Neuron showed that MgT was uniquely effective at raising magnesium concentrations in cerebrospinal fluid and the brain, while other forms failed to meaningfully raise brain magnesium even when they raised serum levels.
In animal models, MgT improved synaptic density in the hippocampus, working memory, short-term and long-term memory retention, and cognitive flexibility. A 2016 RCT by Liu et al. (Journal of Alzheimer's Disease) found that 12 weeks of MgT supplementation significantly improved cognitive function in older adults with cognitive decline. A 2023 study in European Journal of Nutrition found improvements in executive function and attention in healthy middle-aged adults.
Best use cases: Cognitive performance, memory and focus, neurological longevity, older adults with cognitive concerns.
Head-to-Head Comparison
| Glycinate | Threonate | |
|---|---|---|
| Best for | Sleep, anxiety, overall | Cognition, memory |
| GI tolerance | Excellent | Excellent |
| Human data | Moderate | Emerging, promising |
| Cost | Moderate | High |
| Dose (Mg element) | 200-400mg | 144mg (standard) |
Which Should You Take?
Take glycinate if: Sleep is your primary issue, you have anxiety or chronic stress, you're looking for a daily foundational supplement, or budget matters.
Take threonate if: Cognitive performance is your primary concern, you're over 50 and focused on neurological longevity, or you're already handling sleep and recovery well.
Consider taking both if: You're serious about optimization across sleep AND cognition. Many practitioners recommend glycinate at night and threonate in the morning.
Practical Protocol
For sleep: Thorne Magnesium Bisglycinate — 200-400mg elemental magnesium, 30-60 minutes before bed. Third-party tested, clean label.
For cognitive longevity: Momentous Magnesium Threonate — 1.5-2g of MgT or 3 capsules, in the morning. Informed Sport certified and well-dosed.
Start with glycinate. Add threonate if you want the cognitive angle and budget allows. Track your sleep quality, morning HRV, and any muscle cramping — you'll know within 2-3 weeks if you were deficient.