Firoz & Graber 2001: Bioavailability of US Commercial Magnesium Preparations

Purpose

Firoz and Graber set out to address a practical clinical question: do commonly sold magnesium supplements differ enough in absorption that the choice of salt matters? Magnesium deficiency is associated with a range of cardiovascular and metabolic outcomes, and oral supplementation is the standard first-line response in mild-to-moderate hypomagnesemia. Yet retail shelves carry multiple magnesium salts at very different price points, and prescribers rarely have head-to-head evidence to guide selection.

Design

The investigators conducted an open-label randomized crossover trial in 16 healthy adults. Each participant received four commercial preparations — magnesium oxide, magnesium chloride, magnesium lactate, and magnesium aspartate — in randomized sequence with washout periods between doses. The primary outcome was 24-hour urinary magnesium excretion measured before and after each dose. Because the kidney clears excess absorbed magnesium efficiently, urinary excretion is an accepted indirect marker of intestinal absorption when serum levels are stable.

Key Findings

Magnesium oxide produced the smallest rise in urinary magnesium excretion of the four salts tested. The chloride, lactate, and aspartate forms each produced a substantially larger rise, and the three were roughly comparable to each other. The authors estimated fractional absorption of magnesium oxide at approximately one-quarter that of the other preparations. This is clinically meaningful because magnesium oxide carries the highest elemental magnesium content per unit mass — roughly 60 percent — and is therefore the cheapest source of milligram-equivalent dose, which has historically driven its prescribing.

Limitations

The trial is small, open-label, and uses an indirect bioavailability marker rather than direct intestinal absorption measurement (such as a stable isotope balance study). The four salts were tested at equivalent elemental magnesium doses but in single-dose conditions, so the findings do not directly speak to steady-state absorption with chronic dosing or to absorption in patients with gastrointestinal disease. The product samples reflected US market formulations available in 2001 and excipient differences between brands could contribute to the observed effects.

Takeaway

Despite its limitations, this paper is among the most-cited references on practical magnesium salt selection. Its finding that magnesium oxide is poorly absorbed has been corroborated by subsequent work — notably Walker et al. (2003), which extended the comparison to citrate — and it explains a common clinical observation: high-dose magnesium oxide regimens often produce osmotic diarrhea while failing to correct serum magnesium. For supplementation aimed at correcting deficiency, organic salts (chloride, lactate, citrate, glycinate) are generally preferred over oxide on absorption grounds.