Iron

Iron is the most consequential mineral to get wrong. Deficiency is the most common nutritional deficiency worldwide, causing anemia, fatigue, and impaired cognition. But supplementation in non-deficient individuals is uniquely dangerous — iron overload causes liver cirrhosis, heart failure, diabetes, and accelerates oxidative damage. No other essential nutrient has such a narrow therapeutic window between deficiency and toxicity.

The mechanism is tightly regulated. The body has no physiological mechanism to excrete excess iron. Absorption is controlled by hepcidin, a liver-derived peptide hormone that rises with iron sufficiency and inflammation. When hepcidin is high — as it is in iron-replete individuals or during infection — intestinal iron absorption is actively blocked. This is an evolutionary protection against iron overload and against feeding pathogenic bacteria that require iron for growth. Taking iron supplements when hepcidin is elevated wastes money and may increase infection risk.

The trial evidence supports a nuanced approach. Stoffel et al. (2017) published two randomized trials in The Lancet Haematology that changed clinical practice: alternate-day dosing (e.g., 65mg every other day) produced comparable or greater fractional iron absorption than daily dosing, with significantly fewer gastrointestinal side effects. The mechanism is hepcidin-mediated — daily dosing raises hepcidin on day 1, which blunts absorption on day 2; alternate-day dosing allows hepcidin to fall between doses, maintaining higher absorption efficiency.

For formulation, Milman et al. (2015) showed ferrous bisglycinate at 25mg was as effective as ferrous sulfate at 50mg for preventing iron deficiency in pregnancy, with better gastrointestinal tolerability. Bisglycinate is an amino acid chelate that causes less nausea, constipation, and abdominal pain than sulfate — the most common reasons patients abandon iron therapy.

The infection risk is real and underappreciated. Plessis et al. (2013) meta-analysis in JAMA found iron supplementation in children increased diarrhea risk by 11% and respiratory infections in malaria-endemic regions. The mechanism is straightforward: bacteria and parasites require iron for proliferation, and high serum iron during supplementation provides a growth substrate when immune defenses are challenged.

The honest framing: do not take iron without confirmed deficiency. The appropriate workup is ferritin (<30 ng/mL suggests deficiency, <15 ng/mL confirms it), hemoglobin, transferrin saturation, and total iron binding capacity. “Tired all the time” has dozens of causes — B12 deficiency, hypothyroidism, sleep apnea, depression — and iron is only one. In undiagnosed hemochromatosis carriers (1 in 200-400 people of Northern European descent), iron supplementation accelerates organ damage silently.

Practical guidance: if deficient, 25-65mg elemental iron on alternate days, morning, on an empty stomach with vitamin C. Recheck ferritin in 8-12 weeks. Target ferritin >30 ng/mL for general health, >50 ng/mL for athletes and those with restless legs. Once replete, stop supplementing and maintain through diet. Never take iron “just in case.”