Despite being the most common nutritional deficiency with straightforward management, iron deficiency remains largely overlooked and under-treated.

A new study published on Aug. 15 in Blood Advances found that three years after its detection, close to 60 percent of hospital patients still had iron deficiency.

The researchers said the high rates of unresolved iron deficiency cases may be due to clinicians’ inability to recognize laboratory evidence of iron deficiency, possibly due to following reference values that do not detect the condition. It’s also possible they are unaware of the symptoms of iron deficiency without anemia.

Researchers also attribute the delay in resolution to ineffective treatment delivery. For instance, some people are intolerant of oral iron. Other potential contributors include insurance coverage delays and delayed treatment.

“Two years is too long and well beyond the timeframe within which iron deficiency should be able to be sufficiently treated and resolved,” Dr. Jacob Cogan, the study’s lead author and an assistant professor of medicine at the University of Minnesota, said in a statement.

The authors believe that iron deficiency is more widespread than previously recognized, noting that many patients experience significant detriment to their daily functioning. They stated that the findings underscore the urgent need for a more coordinated effort to identify and treat iron deficiency.

“The numbers are pretty striking and suggest a need to put systems in place to better identify patients and treat them more efficiently,” Cogan said.

Researchers reviewed electronic medical record data from a Minnesota health system from 2010 to 2020.

Less than half (41.9 percent) of patients resolved their iron deficiency, with ferritin levels of at least 50 nanograms per milliliter (ng/mL).

On average, iron deficiency takes about two years to resolve. Patients who were male, aged 60 or older, treated with intravenous (IV) iron, and those who had Medicare tended to have a greater chance of resolving their deficiency.

Conversely, blacks, females, and those who did not receive any iron supplementation as treatment were more likely to experience delayed resolution or persistent iron deficiency.

Role of Iron in the Body

Iron is an essential nutrient that is involved in many important processes. Our bodies use it to form hemoglobin, a protein in red blood cells that transports oxygen, and myoglobin, which supplies oxygen to muscles.

Many enzymes in the body require iron to function, including those involved in converting nutrients into energy and producing collagen, neurotransmitters, and hormones. Iron also plays a crucial role in regulating the immune system.

Iron deficiency occurs when iron stores in the body are depleted. It is a broader condition that occurs before anemia develops.

“The severity of iron deficiency and the rate at which it progresses will depend upon the starting iron stores a person has, as well as any bleeding or the underlying etiology (cause) of iron deficiency,” Dr. Jennie Stanford, an obesity medicine specialist who was not involved in the study, told The Epoch Times.

“Iron deficiency begins by depleting stores, and this may or may not cause anemia at this stage. For any further iron losses, it is pulled from the circulation, and that is where anemia can present as a result of iron deficiency,” she said.

Iron deficiency has three stages, with a patient still meeting normal hemoglobin standards (nonanemic) during the first two. The stages are as follows:

• Mild iron deficiency: The body’s iron stores are depleted, but hemoglobin levels are not yet affected
• Marginal iron deficiency: Iron stores are low enough to affect the production of red blood cells
• Iron deficiency anemia: There isn’t enough iron to make hemoglobin for the red blood cells

Nonanemic iron deficiency or iron deficiency without anemia is at least twice as common as iron deficiency anemia.

Iron Deficiency: A Diagnostic Challenge

Iron deficiency can be challenging to detect and often goes unrecognized.

While missed diagnosis is not the only reason some patients’ iron deficiencies are not resolved, researchers in the study said doctors may miss nonspecific iron deficiency symptoms. Clinicians may assume that only iron deficiency with anemia has clinical significance.

They also said that diagnosing iron deficiency can be difficult due to the failure to obtain and correctly interpret all necessary lab tests or because existing lab reference values may inaccurately categorize results as normal.

Clinical guidelines for iron deficiency are inconsistent and lack well-defined diagnostic criteria, causing U.S. clinical guidelines and practices to vary, according to a 2022 study exploring the limitations in guidelines, data, and monitoring of iron deficiency in the United States.

Additionally, the 2022 study showed that many guidelines are based on outdated U.S. Centers for Disease Control and Prevention 1998 recommendations.

Current guidelines use anemia as a proxy for assessing iron deficiency and rely on anemia screening that assesses hemoglobin levels. However, this only detects iron deficiency anemia, overlooking the earlier stages of iron deficiency. This results in up to 70 percent of deficiency cases being missed, particularly among at-risk groups.

There isn’t a standard guideline that everyone uses, Dr. Amar Kelkar, a hematologist at the Dana-Farber Cancer Institute in Boston, Massachusetts, and delegate for the American Society of Hematology, told The Epoch Times in an email.

According to the National Institutes of Health, measuring a person’s serum ferritin concentration, which reflects the body’s iron stores, is a cost-efficient and accurate way to assess iron deficiency.

The World Health Organization defines low ferritin as below 15 micrograms per liter (µg/L) for adults and below 12 µg/L for children. However, in clinical practice, a threshold of below 30 micrograms per liter is often used due to its higher sensitivity and specificity for detecting iron deficiency.

Some studies have shown that ferritin levels may not always accurately reflect iron levels, as they tend to be elevated in older people and individuals with inflammatory conditions, such as infections or chronic inflammation, including inflammatory bowel disease.

“Ferritin is an imperfect parameter,” Kelkar said, adding that people who are iron deficient do not seem to have as much of a rise in ferritin in inflammatory states. “I consider ferritin more of a rule out test (i.e., people with high ferritin very rarely are concurrently iron deficient).

The study authors said they could not determine patients’ inflammation status, which could have elevated ferritin levels in some individuals. This raises the possibility that some patients with iron deficiency may have been incorrectly classified as having sufficient iron levels. The authors did not mention the impact of ferritin levels on older adults among the study’s limitations.

The authors also stated that ferritin value alone is insufficient to evaluate iron deficiency thoroughly. A more accurate assessment involves a combination of tests, including hemoglobin and ferritin levels and transferrin saturation.

Symptoms of Iron Deficiency

People with iron deficiency may not show symptoms until their iron stores become depleted, affecting red blood cell production and leading to anemia. At this point, symptoms may begin to appear.

Iron deficiency may cause unexplained, nonspecific symptoms that clinicians may not initially recognize as being due to iron deficiency. These include:

• Cognitive problems such as fatigue, headache, absentmindedness, poor cognitive function, impaired memory, depression, and sleep disturbance
• Cardiorespiratory issues such as palpitations, shortness of breath, and reduced exercise performance
• Muscular and connective tissue problems such as weakness, muscle and joint pain, dry skin, and restlessness
• Hair loss
• Cravings to chew ice
• Compulsive swallowing of nonfood items
• Weight gain

“Iron deficiency can also lead to fatigue, less ability to work, and difficulty doing physical activities. In children, iron deficiency can lead to problems with brain development that may be irreversible. If left untreated, iron deficiency will get worse and can lead to iron deficiency anemia,” a spokesperson for the Centers for Disease Control and Prevention’s Division of Nutrition, Physical Activity, and Obesity, told The Epoch Times.

Recognizing and Treating Iron Deficiency

Clinicians emphasize the importance of treating iron deficiency even without anemia or symptoms. Additionally, a person may have significantly low iron levels despite normal hemoglobin and a complete blood count.

They also recommend beginning iron deficiency treatment immediately upon diagnosis, especially in symptomatic individuals. Treatment should continue until ferritin levels are normalized (>100 µg/L) and symptoms have resolved.

Guidelines recommend monitoring ferritin levels every six to 12 months after treatment, especially in at-risk groups. Continuous monitoring ensures a person’s iron level remains stable and that they receive treatment if it drops again.

The choice between oral or IV iron depends on factors such as the individual’s age, sex, cause of iron deficiency, and the duration of the condition (long-standing versus recent). If oral supplementation is not enough or is poorly tolerated, clinicians may offer IV iron instead of oral.

“While oral iron is the preferred method of replacement for reasons like menstrual losses or other non-severe bleeding, oral iron is not ideal for iron deficiency that is caused by malabsorption, as it would be unlikely to be absorbed,” Stanford told The Epoch Times via email.

Furthermore, it can be dangerous to take iron supplements outside of a doctor’s recommendations because it may lead to overconsumption. Too much iron can reduce zinc absorption and cause gastrointestinal symptoms such as constipation, diarrhea, and vomiting.

Taking doses of 20 to 60 milligrams per kilogram (mg/kg) can be mildly to moderately toxic, and intake of more than 60 mg/kg may lead to more serious side effects, including shock, multisystem organ failure, and even death.

“In cases of mild iron deficiency that are not caused by malabsorption, consuming additional dietary iron can be helpful in resolving iron deficiency,” Stanford wrote.

Meats such as pork, chicken, beef, and eggs provide heme iron, the type most readily absorbed by our bodies (around 30 percent). In contrast, nonheme iron, found in plant-based foods such as fruits, vegetables, and nuts, is absorbed at a lower rate (around 10 percent). Consuming foods high in vitamin C can enhance the absorption of nonheme iron.

Update: The article has been updated with comments from the CDC and Amar Kelkar.