Fibromyalgia, Low Iron, and Mitochondrial Health: What Is the Connection?

Fibromyalgia is a chronic condition associated with widespread pain, fatigue, unrefreshing sleep, and cognitive difficulties. While its underlying causes are complex, research suggests that iron status and mitochondrial function may be important considerations when evaluating persistent fatigue and pain.

Iron Deficiency and Fibromyalgia

Iron is essential for oxygen transport, energy production, and neurotransmitter synthesis. Low iron stores can contribute to fatigue, reduced exercise tolerance, cognitive difficulties, and restless legs—even when hemoglobin levels remain normal.

A case-control study comparing 46 women with fibromyalgia with 46 healthy controls found significantly lower average ferritin levels in the fibromyalgia group. The researchers suggested that low iron stores may be associated with fibromyalgia, although the study could not establish cause and effect.

Importantly, a separate randomized, placebo-controlled trial investigated intravenous ferric carboxymaltose in 80 iron-deficient patients with fibromyalgia. The treatment group showed improvements in several measures of symptom severity, pain, and fatigue, although the difference in the primary responder outcome was not statistically significant.

These findings suggest that identifying and treating iron deficiency may be worthwhile in selected patients, but they do not establish iron supplementation as a treatment for fibromyalgia itself.

Mitochondria and Cellular Energy

Mitochondria are structures within cells that generate ATP, the energy needed for normal cellular function. Researchers have proposed that impaired mitochondrial function and oxidative stress may contribute to fatigue and pain in fibromyalgia.

A 2024 study published in Scientific Reports evaluated mitochondrial function in blood cells from 50 patients with fibromyalgia and 20 healthy controls. Researchers found a lower bioenergetic health index in the fibromyalgia group, with greater impairment associated with more severe symptoms.

Earlier research has also reported changes in mitochondrial membrane potential, coenzyme Q10 levels, and markers of oxidative stress in people with fibromyalgia. However, findings vary across studies, and it remains uncertain whether these abnormalities are causes, consequences, or contributing factors in the condition.

How Are Iron and Mitochondria Connected?

Iron is required for several proteins involved in the mitochondrial electron transport chain, which helps generate ATP. When iron deficiency is present, cellular energy production can be affected.

This provides a biological rationale for investigating iron status in people experiencing persistent fatigue. However, there is not yet sufficient evidence to conclude that low iron causes mitochondrial dysfunction in fibromyalgia or that correcting iron levels will resolve fibromyalgia symptoms.

What Should Patients Consider?

For individuals with fibromyalgia and persistent fatigue, a clinician may consider evaluating:

• Iron status: Complete blood count, ferritin, and transferrin saturation when appropriate.
• Other contributors to fatigue: Thyroid dysfunction, vitamin B12 deficiency, sleep disorders, and other relevant conditions.
• Individualized treatment: Correcting confirmed deficiencies and monitoring whether symptoms and functional capacity improve.

Iron supplementation should be guided by laboratory findings and clinical assessment. Excess iron can be harmful, and the cause of iron deficiency—such as blood loss or impaired absorption—should be investigated when indicated.

The Bottom Line

Research suggests that low iron stores and altered mitochondrial function may be relevant in some people with fibromyalgia. Addressing a documented iron deficiency may improve associated fatigue and other symptoms, while mitochondrial dysfunction remains an active area of investigation.

A comprehensive approach should focus on identifying treatable contributors to symptoms without assuming that one mechanism explains fibromyalgia in every patient.

This article is for educational purposes only and is not a substitute for individualized medical advice.

References

1. Ortancil O, et al. Association between serum ferritin level and fibromyalgia syndrome. European Journal of Clinical Nutrition. 2010;64:308–312.
2. Arnold LM, et al. A blinded, randomized, placebo-controlled study to investigate the efficacy and safety of ferric carboxymaltose in iron-deficient patients with fibromyalgia. Rheumatology and Therapy. 2018;5:271–281.
3. Macchi C, et al. Mitochondrial function in patients affected with fibromyalgia syndrome is impaired and correlates with disease severity. Scientific Reports. 2024;14:30247.
4. Cordero MD, et al. Mitochondrial dysfunction and mitophagy activation in blood mononuclear cells of fibromyalgia patients: implications in the pathogenesis of the disease. Arthritis Research & Therapy. 2010;12.
5. Ho T, Ryan M, Holle J. Redox reactions in chronic pain: mechanisms and relevance in fibromyalgia. Frontiers in Pain Research. 2025;6:1593908.