Can iron overload cause magnesium absorption issues?

Iron Overload and Magnesium Absorption

Iron overload does not cause magnesium absorption issues; rather, the relationship works in the opposite direction—magnesium can potentially interfere with iron absorption, though this effect is inconsistent and clinically insignificant in humans.

The Directional Relationship Between Iron and Magnesium

The available evidence demonstrates that magnesium affects iron metabolism, not the reverse:

• Magnesium can competitively inhibit iron absorption through the divalent metal transporter 1 (DMT1), which is responsible for absorbing both iron and magnesium in the duodenum 1
• Calcium can inhibit DMT1 in a dose-dependent manner to reduce iron absorption, and low magnesium concentrations can exacerbate iron deficiency, suggesting magnesium competes at the same transporter 1
• However, clinical trials in humans have failed to demonstrate meaningful reduction in iron absorption when high-dose magnesium is administered 2

Evidence from Human Studies

The human data directly contradicts any concern about iron affecting magnesium:

• In a controlled trial of 15 patients with hereditary hemochromatosis (C282Y homozygotes), treatment with 809.6 mg of oral magnesium every 8 hours for two weeks showed no significant difference in iron absorption before versus after magnesium treatment (14.7 vs 14.9 micromol/L, P = 0.7) 2
• Studies examining magnesium hydroxide administration after iron overdose in healthy volunteers showed no effect on iron absorption when given at a 5:1 ratio of magnesium to elemental iron 3
• One study did show reduced iron absorption when magnesium hydroxide was given at 4.5 g per gram of elemental iron (a much higher ratio), but this was in the context of acute iron overdose, not chronic iron overload 4

Animal Model Data (Not Applicable to Humans)

• Animal studies in magnesium-deficient rats showed that excess iron intake reinforced iron accumulation in liver and spleen, and these rats had abnormal iron metabolism 5
• This animal model is not relevant to your question because it examines magnesium deficiency causing abnormal iron handling, not iron overload causing magnesium absorption problems 5

Iron Overload Does Not Impair Mineral Absorption

The extensive guideline literature on iron overload focuses on organ damage from iron deposition:

• Iron overload causes organ toxicity through oxidative stress and direct iron deposition in the heart, liver, and endocrine organs, leading to cardiomyopathy, cirrhosis, diabetes, and hypothyroidism 6, 7
• The pathophysiology involves non-transferrin bound iron entering cells through L-type calcium channels when transferrin saturation is exceeded 6, 7
• There is no mention in any major guideline of iron overload causing malabsorption of other minerals, including magnesium 6

Clinical Bottom Line

If you are concerned about a patient with iron overload having low magnesium levels, look for other causes of hypomagnesemia rather than attributing it to the iron overload itself. Common causes include:

• Medications (diuretics, proton pump inhibitors)
• Chronic diarrhea or malabsorption syndromes
• Chronic kidney disease (if the patient is on dialysis for other reasons)
• Alcohol use
• Diabetes with glycosuria

The iron overload itself should be managed with phlebotomy (in non-anemic patients with hereditary hemochromatosis) or chelation therapy (in transfusion-dependent patients), as these interventions improve morbidity and mortality from cardiac and hepatic complications 6, 7.