Iron is required for haemoglobin synthesis, the oxygen transport protein in red blood cells. But iron has a second, equally important role: as a cofactor in cytochrome enzymes in the mitochondrial electron transport chain, it is directly required for ATP synthesis. This means that iron deficiency impairs cellular energy production through mitochondrial dysfunction as well as through reduced oxygen delivery, and this mitochondrial effect occurs with depleted iron stores before haemoglobin levels fall below the clinical anaemia threshold. The consequence is that normal haemoglobin does not exclude iron deficiency as a cause of fatigue.
Ferritin: The Storage Marker That Matters
Ferritin is the protein that stores iron in tissues. Low ferritin indicates depleted iron stores and precedes the development of iron-deficiency anaemia. The laboratory reference range for ferritin in many UK labs starts at 12 to 15 micrograms per litre, values at which iron stores are essentially exhausted. Symptoms of iron deficiency and fatigue have been documented in women with ferritin levels below 50 micrograms per litre in several studies. A ferritin of 20 micrograms per litre may be reported as normal but represents significant iron store depletion with meaningful functional consequences.
Who Is Most at Risk
Women with heavy menstrual bleeding are the highest-risk group, as monthly iron losses can exceed the dietary replacement capacity even on an omnivore diet. Endurance athletes, particularly female runners, are at significant risk due to haemolytic anaemia from foot strike and increased gastrointestinal iron loss. Vegetarians and vegans consume non-haem iron, which is less bioavailable than haem iron from meat and is further inhibited by phytates in whole grains and calcium. Adults with coeliac disease, inflammatory bowel disease, or a history of bariatric surgery have impaired iron absorption.
Absorption Optimisation and Supplementation
If dietary iron is adequate but ferritin remains low, absorption may be the issue. Vitamin C consumed with iron-containing meals increases non-haem iron absorption by three to four fold through reduction of ferric to ferrous iron. Coffee, tea, and calcium consumed within an hour of iron-containing meals significantly reduce absorption. Iron supplements taken on alternate days have better tolerability and comparable absorption to daily dosing according to recent research, as iron absorption is higher when mucosal ferritin has been cleared overnight.
- Request ferritin alongside haemoglobin when investigating fatigue: an optimal ferritin for energy is above 50 micrograms per litre
- Consume vitamin C-rich foods or a supplement alongside iron-rich meals or iron supplements
- Avoid coffee, tea, and dairy within one hour of iron-rich meals or iron supplements
- Alternate-day iron supplementation is better tolerated and may be equally effective to daily dosing
- If ferritin fails to rise with adequate oral supplementation, request investigation for malabsorption
Sources
- Beard, J.L. (2001). Iron biology in immune function, muscle metabolism and neuronal functioning. Journal of Nutrition, 131(2S-2), 568S-580S.
- Moretti, D., et al. (2015). Alternate-day dosing of iron supplementation is preferable to daily dosing in women of reproductive age. Blood, 126(23), 2560-2560.