HomeMedicineInternal MedicineIs Iron-Deficiency Without Anemia a Potential Cause of Fatigue?

Is Iron-Deficiency Without Anemia a Potential Cause of Fatigue?

A recently published study in the British Journal of Nutrition aims to determine whether IDNA is associated as a cause of fatigue and whether iron therapy is effective in treating patients.

Iron deficiency is the most prevalent nutritional deficiency in the world.

Affecting mostly women and children, iron deficiency remains an important medical issue as it can greatly affect an individual’s quality of life.

We need iron to maintain our energy levels, support a healthy immune system, and for our overall mental and physical health. Without enough iron, individuals may feel tired, weak, and apathetic among a range of other symptoms.

Exhausted iron stores may eventually lead to iron deficiency without anemia and further depletion may result in iron-deficiency anemia.

But what exactly is the difference between iron deficiency with and without anemia?

The answer lies in the hemoglobin levels.

Iron and Hemoglobin in Anemia

Hemoglobin is a molecule in red blood cells. It carries oxygen from the lungs to the tissues and returns carbon dioxide from the tissues to the lungs.

Most of our body’s iron stores are found in the blood attached to the hemoglobin molecule. Iron that isn’t attached to hemoglobin circulates in the blood in the form of a protein called ferritin.

Iron deficiency without anemia occurs when iron stores are reduced, but the hemoglobin levels are still above the cut-off value for anemia.

Iron deficiency anemia results when both iron and hemoglobin levels, or red blood cells, are depleted below healthy values.

Fatigue and Iron Deficiency Without Anemia

Since iron deficiency without anemia (IDNA) occurs when only iron stores—not hemoglobin levels—are reduced, is IDNA still associated with fatigue in the same way as anemia?

Previous research studies on the relationship between fatigue and IDNA have been inconclusive.

One study found that IDNA was associated with increased fatigue, while another did not. Another study found that iron therapy had a significant therapeutic effect on fatigue in patients with IDNA, while another did not find a significant association.

A recently published study in the British Journal of Nutrition sought to resolve these controversies by answering the following questions:

  1. Is IDNA associated with fatigue?
  2. If IDNA is associated with fatigue, is iron therapy effective in treating patients with IDNA?

To do so, researchers performed a systematic review of previous research and compared all the study findings via meta-analysis using mathematical methods.

Comparing Previous Research

Researchers probed through the PubMed database for previous studies on fatigue and IDNA published between 1809 and January 2016.

They included 12 studies for further analysis. Six of the studies were randomized controlled trials, meaning the participants were allocated at random to receive one of many clinical interventions.

The other six were cross-sectional studies, which are observational and in which they collect and analyze data from a population at a specific point in time. Among the 12 studies, there were a total of 1875 participants, most of which were female.

Significant Therapeutic Effect of Iron Treatment

The researchers found that IDNA is indeed associated with fatigue. However, it is still unclear how IDNA can be a cause of fatigue.

They also found a significant therapeutic effect of iron treatment in fatigue patients with IDNA.

However, they did not find a significant effect among the cross-sectional studies at first. It was only after they removed one study did the outcomes became significant.

This is because the study they removed was based on an unscreened population from the community, whereas the other studies were based on screened participants for interventional trials or patients with a certain disease.

The researchers note that further studies are needed to determine the diagnostic criteria to select patients who might benefit from iron treatment and whether the association between fatigue and IDNA also exists in the general population, outside of those with certain diseases. 

Large randomized controlled trials are needed to confirm a cause-and-effect relationship between iron supplementation and fatigue.

Written by Jessica Gelar

Reference: Yokoi K and Konomi A. Iron deficiency without anemia is a potential cause of fatigue: meta-analyses of randomized controlled trials and cross-sectional studies. British Journal of Nutrition. 2017 May 11.


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Jessica Gelar HBSc
Jessica Gelar HBSc
Jessica has an HBSc from the University of Toronto with a double major in Biology for the Health Sciences and Professional Writing and Communication. She is interested in global and public health and is passionate about bringing the latest research news to the public so that readers can be well-informed when making health-related decisions. As part of the Medical News Bulletin team, Jessica hopes to bridge the gap between scientists and the general public by breaking down scientific jargon into a simple narrative.


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