Iron Deficiency and Mental Health
Key points
Iron deficiency is the most common nutritional deficiency worldwide and is associated with depression, anxiety, and attentional symptoms — often before anemia appears.
Serum ferritin is the most useful single test, but it is an acute-phase reactant; pair it with transferrin saturation when inflammation is possible.
Diagnostic cutoffs are still not defined: the WHO uses 15 µg/L, while sleep medicine guidelines point toward 75–100 µg/L.
The lack of a clear direction makes it difficult to determine who to treat and what the target of treatment should be.
Treating iron deficiency may improve psychiatric outcomes, but the supplementation evidence is still mixed — and an underlying cause should always be sought.
Intro + Why is this important?
Iron is an essential element for multiple functions in the human body. At the same time, iron deficiency is the most common nutritional deficiency worldwide. Beyond facilitating oxygen transport by red blood cells, iron is a cofactor for the synthesis of monoamine neurotransmitters, synaptogenesis, and myelin synthesis. It is therefore not surprising that iron deficiency is associated with several neuropsychiatric symptoms. With a prevalence of iron deficiency as high as 10% in the pediatric population and 17.4% in premenopausal females, it is important that psychiatrists become acquainted with the different clinical manifestations of iron deficiency.
Iron deficiency, even without overt anemia, can cause, contribute to, or mimic several symptoms of psychiatric disorders. Therefore, psychiatrists should be familiar with the manifestations and risk factors for iron deficiency. Moreover, there is evidence that treating iron deficiency can improve the efficacy of psychiatric treatment and lead to better outcomes.
Psychiatric Symptoms of Iron Deficiency
Fiani (Nutrients, 2024) showed an increased association of iron deficiency with depressive symptoms (higher PHQ-9 scores), worse mental well-being, and more severe anxiety in an adolescent population. A similar finding was replicated by Hassan et al. (Frontiers in Psychiatry, 2025). Even in samples with no psychiatric diagnosis, Karatepe et al. found an increased risk of alexithymia and anxiety, and a lower quality of life, in women with iron deficiency anemia compared to controls with no iron deficiency. Importantly, the presence of a psychiatric diagnosis was an exclusion criterion for this study, meaning that even in a population with no co-existing psychiatric diagnosis, iron deficiency anemia is associated with an increased risk of several psychiatric symptoms and a lower quality of life.
On a population level, Gottfried (2013) found lower ferritin levels in a community mental health clinic versus a national sample. Sørensen (2011) and Insel (2008) also found an increased risk of schizophrenia spectrum disorders in offspring born to mothers with anemia.
In summary, iron deficiency is a well-established contributor to several symptoms, including difficulty concentrating, anxiety, low energy, and low mood.
TL;DR: There does appear to be a correlation between lower iron levels and psychiatric symptoms. Sometimes, these symptoms look a lot like depression, ADHD, sleep problems or anxiety.
Definitions, Biochemical Investigations, and Clinical Pearls
To get a better understanding of the strengths and weaknesses of the different tests that assess iron status, it is important to review the different physiological functions of the currently available biomarkers. First, anemia is defined as low hemoglobin. To determine whether anemia is present, a CBC is necessary. On a CBC, the MCV and MCHC can help determine red blood cell (RBC) size and hemoglobin concentration, and suggest a cause for the iron deficiency. Low MCV and MCHC are associated with iron deficiency, whereas an elevated MCV can point to B12 or folate deficiencies. Other commonly ordered tests are ferritin, transferrin, transferrin saturation, and serum iron. Serum ferritin is the body's physiological iron store and the most commonly cited lab test in the literature to diagnose iron deficiency. Ferritin is also an acute-phase reactant, so if a patient has an exacerbation of a chronic condition (for example, an exacerbation of Crohn's disease), a recent infection, or a metabolic stressor (such as surgery), serum ferritin levels will be higher and will not accurately reflect the body's iron concentration. In these situations, ordering the percentage saturation of the iron-transporting protein (transferrin) can help determine whether iron deficiency is present. In general, ferritin levels do not require fasting, but serum iron and transferrin do require the patient to fast for 12 hours prior to the sample being drawn. Additionally, using discounted lab networks, the total out-of-pocket cost for a CBC, ferritin, transferrin, serum iron, and binding capacity is approximately $58. Depending on the patient's insurance coverage, the cost may be higher or lower than this.
Importantly, the biochemical definition of iron deficiency is still to be established, especially in populations without overt anemia. For example, the WHO uses a cutoff of 15 µg/L as the biochemical definition of iron deficiency, but the American Academy of Sleep Medicine (AASM) uses a much higher threshold of 75–100 µg/L as the minimum that should be achieved to optimize iron status. This is because preliminary reports appear to indicate that brain iron levels decrease before serum levels. In practice, a cutoff of 75 µg/L — especially in light of symptoms — is usually optimal.
TL;DR: Ferritin is usually the best test to screen for iron deficiency, however correctly interpreting ferritin levels involves understanding a full clinical context.
Treatment Implications
A 2024 meta-analysis of nine studies of iron supplementation in ADHD found a large effect size for hyperactivity (Cohen's d = 1.7); however, the response to placebo was also significant (Cohen's d = 0.76). Heterogeneity among the studies was high, blinding and allocation to treatment were not well described for most of the studies, and both the placebo and the iron-supplementation effect sizes crossed the null-hypothesis threshold, meaning the pooled effect sizes were not statistically significant. Results were similar for inattentive symptoms. This same meta-analysis reported an RCT exploring iron supplementation for sleep in an ASD population; with a small sample size (n = 20), it found no statistically significant differences in the primary outcomes, but a change of 1.5 on the sleep CGI score, albeit with no changes in daytime functioning. Additionally, a recent meta-analysis showed improvements in anxiety, well-being, short-term memory, and intelligence (Cohen's d between 0.34 and 0.53), with improvement in depression scores only in those who were previously iron deficient. For mood and anxiety, Fiani et al. reported mixed findings, with some studies suggesting a significant effect on anxiety but not on mood, and pre-post studies suggesting a significant effect on depression.
TL;DR Though the evidence is contradictory, iron supplementation does appear to benefit psychiatric symptoms when they are caused by iron deficiency.
Supplementation and Recommendations
Although iron deficiency is common, especially in high-risk populations, it is important to consider its possible causes. Therefore, co-managing with a person's primary care physician, pediatrician, or hematologist is crucial. Autoimmune conditions, adenomas of the colon, or occult bleeding due to neoplastic disease can be missed. The risk is higher in populations that do not get enough iron in their food (for example, patients with restricted diets, such as vegetarians and vegans, or those with an ARFID or ASD diagnosis) or who have increased blood loss (such as frequent blood donors and premenopausal women). Additionally, Black and Latinx populations appear to be at higher risk for iron deficiency on a population level.
In general, levels below 75 µg/L appear to benefit more from intravenous (IV) repletion, however, oral therapy is still possible. Here are a few supplements I have recommended before and have found them clinically effective and well-tolerated
Megafood Iron Builder
Iron Bisglycinate or Advanced Iron Complex by Thorne
Pure Encapsulations Iron-C
For oral therapy, usually every other day treatment is just as (sometimes more) effective than daily iron.
Summary:
Iron deficiency is common, especially in premenopausal women, black and latino population.
Iron deficiency can present without overt anemia.
Iron deficiency can potentially cause, or worsen mood, anxiety, focusing and energy symptoms.
Iron repletion can be done orally and intravenously, depending on the causes, levels and symptoms. There are several well-tolerated formulations.
The information in this article is provided for general educational purposes only and does not constitute medical advice. It is not a substitute for professional diagnosis, treatment, or the advice of a qualified healthcare provider, and reading it does not create a physician–patient relationship. Always consult your own physician or a qualified clinician about your specific situation. If you are experiencing a medical emergency, call 911 or go to the nearest emergency room.