Ferritin stores iron and transports it to where it is required. In blood, it is an important indicator of the total iron stores. However, ferritin also participates in infections, inflammation, and malignancies. Elevated ferritin is often found in disorders with chronic inflammatory states such as obesity, metabolic syndrome, and diabetes. Find out why it is important to keep this protein in balance, and which factors increase or decrease ferritin levels.
- Joe’s Experience With Ferritin
- Recommended Supplements for Increasing Ferritin/Iron Status Without Gut Problems
- Optimal Reference Range for Ferritin
- Diseases Associated With Higher Ferritin
- Ferritin is Elevated in Anemia of Chronic Disease (ACD)
- Higher Ferritin is Associated With Diabetes
- Higher Ferritin is Associated with Metabolic Syndrome
- High Ferritin is Associated With Atherosclerosis
- Ferritin is Elevated in Anorexia
- Ferritin is Higher in Grave’s
- High Ferritin May Contribute to Heart Arrhythmia
- Higher Ferritin is Associated With Cancer (most of the time)
- Ferritin is High in Sideroblastic Anemia
- Higher Ferritin is Associated With Fatty Liver (NAFLD)
- Higher Ferritin is Associated With Liver Damage in Hepatitis C
- Ferritin is High in Still’s Disease
- Ferritin is High in Hemochromatosis
- Ferritin is Extremely High in Hemophagocytic Syndrome
- Diseases Associated With Lower Ferritin
- Low Ferritin Indicates Anemia
- Low Ferritin is Associated With Fatigue
- Ferritin is Lower in Fibromyalgia
- Ferritin is Lower in IBD
- Ferritin is Lower in Hypothyroidism
- Ferritin is Lower in Depression and Anxiety
- Low Ferritin Causes ADHD
- Ferritin in Neurodegenerative Diseases
- Ferritin is Lower in Celiac Disease
- Ferritin in Restless Legs Syndrome
- Factors that Elevate Ferritin
- Factors that Decrease Ferritin
- Recommended Supplements for Increasing Ferritin/Iron Status Without Gut Problems
Ferritin is a spherical protein complex. It is the primary iron-storage protein within the cell, that stores iron in a soluble, non-toxic form, and can transport it to areas where it is required (R).
Iron can be toxic to cells because of its capacity to generate reactive species which can directly damage DNA and proteins. Ferritin captures and buffers the iron within cells, and is very important for our survival (R).
Mice deficient in ferritin die in the embryo stage (R).
Ferritin is found in most tissues where it is located inside the cells. Within the cells, ferritin is mostly found in the cellular fluid (cytosol), nucleus or mitochondria (R).
Mitochondrial ferritin (FtMt) is produced by specific tissues such as the testis and the brain (R).
Small amounts of ferritin are also secreted into the blood where it functions as an iron carrier. Apart from the blood, ferritin is also secreted into joint (synovial) and spinal fluids (R).
The liver’s stores of ferritin are the primary source of reserve iron in the body (R).
As previously mentioned, ferritin plays an important role in the storage of cellular iron (R). It functions in cell detoxification, limiting the formation of reactive oxygen species, and mitigating their damaging effect on cellular structures (R).
By capturing toxic metal ions, ferritin is involved in the antioxidant system of cell defense. Apart from iron, ferritin also regulates the cellular concentration of other transition metals, including beryllium, aluminum, zinc, cadmium and lead (R).
On the other hand, ferritin outside the cell can function as a highly efficient iron delivery mechanism. Compared to another iron carrier – transferrin, which carries a maximum of 2 iron atoms, a single ferritin molecule can sequester up to 4500 iron atoms (R).
Blood ferritin, which is believed to be iron-poor, carries much less iron than this, but could nevertheless make a significant impact on iron delivery (R).
Ferritin acts as a buffer against iron deficiency and iron overload (R).
Additionally, it was shown that circulating ferritin may assume roles entirely independent of its classic role as an iron binding protein (R).
Ferritin is may play an important role in the skin defence. Ferritin in the skin is increased by UVA and infrared-A radiation. Increased ferritin following acute UV/IR radiation could afford increased protection against subsequent oxidative stress (R,R).
Ferritin is an acute phase reactant and a marker of acute and chronic inflammation and is nonspecifically elevated in a wide range of inflammatory conditions (R).
One study suggests that blood ferritin actually originates from damaged cells and thus reflects cellular damage (R).
Ferritin has also been shown to suppress immune activity in humans (R).
Ferritin can stimulate blood vessel growth in inflammation, desirable in wound healing, but undesirable in tumors (R).
Unless indicated otherwise, the statements in the text below refer to the circulating ferritin found in blood.
Joe’s Experience With Ferritin
Most of my client population have lower ferritin and this is usually because of some kind of intestinal inflammation that is not allowing the person to absorb iron well, as well as hypothyroidism.
When iron (indicated by ferritin) is lower, it can contribute to and exacerbate existing health problems, so you want to get that fixed.
I myself had ferritin on the lower end of the range when I wasn’t as healthy (about 40-50).
Some people are trying to get ferritin to 20 ng/ml for “anti-aging purposes”, but given the research cited here, that’s a big mistake.
I personally try to get my ferritin levels over 90 ng/ml, especially because I’m Th1 dominant and more iron is better for me.
Recommended Supplements for Increasing Ferritin/Iron Status Without Gut Problems
- Preferred: Ferric iron polymaltose complex + heme iron polypeptide (R)
- Heme iron polypeptide (R)
Optimal Reference Range for Ferritin
Blood ferritin is an indirect indicator of the total amount of iron stored in the body. Therefore, blood ferritin is used as a diagnostic test for iron-deficiency anemia (R).
Ferritin is normally high at birth. Ferritin levels rise during the first two months of age and then fall until the end of the first year of life, i.e. later infancy. At about one year of age, ferritin levels begin to rise again (R).
Normal ferritin blood levels:
- Men: 18-270 or 30-300 nanograms per milliliter (ng/mL)*
- Women: 18-160 or 10-200 ng/mL*
- Children (6 months to 15 years): 7-140 ng/mL
- Infants (1-5 months): 50-200 ng/mL
- Newborns: 25-200 ng/mL
- reference ranges for blood ferritin vary across laboratories, but generally levels of 30 to 300 ng/ml are considered normal for men, and 10–200 ng/ml for women (R).
Note that ferritin has been shown to increase in response to stress, such as inflammation or infection. These conditions may change what would otherwise be low ferritin indicating a lack of iron, into a value in the normal range.
Because it also behaves as an acute phase protein, the levels of ferritin can go up several-fold in response to stress and infections or inflammatory states (R). In these cases, ferritin stops being an accurate indicator of iron deficiency.
Some studies state that the traditional cutoff point of 12 and 30 ng/ml is too low to detect iron deficiency anemia in the general population, but especially for those with inflammatory or liver diseases. A level higher than approximately 40 ng/ml was suggested to exclude iron deficiency in most patients, and a level higher than 70 ng/ml was suggested to exclude iron deficiency in patients with inflammation or liver diseases (R).
Vegetarians can have significantly lower blood ferritin levels, resulting from iron deficiency. One study found iron deficiency in 19% of vegetarians (R).
If ferritin is high, there is iron in excess or else there is an acute inflammatory reaction in which ferritin is mobilized without iron excess.
Ferritin is increased under oxidative stress. It is increased by the antioxidant-responsive element (ARE) (R). Ferritin, in turn, can increase liver proinflammatory mediators IL-1b, iNOS, RANTES, IkappaBα, and ICAM1 (R).
Ferritin is used as an indicator for iron overload disorders, such as hemochromatosis or hemosiderosis.
As ferritin is also an acute-phase reactant (a part of body’s response to inflammation), it is often elevated in various diseases. A normal C-reactive protein (CRP) can be used to exclude elevated ferritin caused by acute phase reactions.
Ferritin levels of greater than 1000 ng/ml are a nonspecific marker of illness, including infections and cancer (R).
However, ferritin over 300 can indicate some inflammation.
Diseases Associated With Higher Ferritin
Circulating ferritin is widely recognized as an acute phase reactant and a marker of acute and chronic inflammation. It is elevated in a wide range of inflammatory conditions, including chronic kidney disease, rheumatoid arthritis and other autoimmune disorders, acute infections, and malignancy (R).
The elevated ferritin in these states reflects increased total body iron storage, but paradoxically, these stores are sequestered and not available for red blood cell production. This contributes to the widely recognized anemia of chronic disease (ACD) (R).
Note that although ferritin levels generally increase in infection, some infections can also result in decreased ferritin (R).
Ferritin is Elevated in Anemia of Chronic Disease (ACD)
Anemia of Chronic Disease is the most frequent anemia in hospitalized patients. It develops in subjects suffering from diseases that are associated with chronic activation of cell mediated immunity, such as chronic infections, immune mediated inflammatory disorders, or malignancy (R).
A hallmark of ACD is a decrease in available iron, limiting the production of red blood cells. Meanwhile, iron is taken up by macrophages and dendritic cells. Thus ACD can be easily diagnosed by the presence of low iron, but increased blood levels of ferritin (R).
Pure iron deficiency is recognized by low ferritin and transferrin saturation but increased transferrin concentrations. Patients with “classical” ACD present with increased ferritin levels while transferrin concentrations as well as transferrin saturation are reduced. In contrast, all of these parameters are decreased in ACD patients with iron deficiency (R).
Higher Ferritin is Associated With Diabetes
Elevated levels of ferritin may help identify individuals at high risk of type 2 diabetes (R).
In one study, subjects with elevated ferritin had a 2.4-fold higher risk of developing type 2 diabetes (R).
Higher Ferritin is Associated with Metabolic Syndrome
In certain situations, elevated ferritin levels are found in patients with metabolic syndrome (R).
Significant correlations were found between ferritin concentration and metabolic syndrome parameters (HDL cholesterol, triglycerides, and fasting glucose) as well as an increase in the ferritin value with the number of risk factors of metabolic syndrome in healthy men (R).
Also, oxidative stress markers (carbonyl groups, AOPP, and glycated hemoglobin), liver damage markers (GGT, SGOT), and parameters related to insulin resistance (HOMA, blood insulin, and blood glucose) correlate significantly with ferritin (R).
High Ferritin is Associated With Atherosclerosis
It was linked with artery stiffness in apparently healthy Korean women (R).
Ferritin is Elevated in Anorexia
Ferritin is Higher in Grave’s
High Ferritin May Contribute to Heart Arrhythmia
Ferritin and iron levels are associated with electrocardiogram findings in acutely ill patients. High ferritin contributes to abnormal heart electrical activity in a variety of medical conditions, and possibly contributes to the emergence of fatal heart arrhythmias (R).
Higher Ferritin is Associated With Cancer (most of the time)
Although ferritin is elevated in these states, iron stores are not available for producing red blood cells, causing anemia of chronic disease (ACD) (R).
This relative iron deficiency in inflammation and malignancy is presumed to have developed as a defense mechanism to restrict iron utilization by tumors/pathogens (R).
However, some cancers are also associated with low levels of ferritin, such as colon cancer (R).
Ferritin is High in Sideroblastic Anemia
Sideroblastic anemia is a disorder in which there is a failure to produce healthy red blood cells. A common manifestation of sideroblastic anemia is iron overload and elevated ferritin (R).
Higher Ferritin is Associated With Fatty Liver (NAFLD)
Elevated ferritin and mildly increased iron stores are frequently observed in patients with non-alcoholic fatty liver disease (NAFLD), where ferritin increase can reflect oxidative stress, inflammation, and liver tissue death (R).
Ferritin levels were shown to predict NAFLD incidence in healthy Korean men (R).
Higher Ferritin is Associated With Liver Damage in Hepatitis C
Ferritin is High in Still’s Disease
Adult onset Still’s disease is a systemic inflammatory disorder characterized by fever, arthritis, and rash, that typically affects young women. Elevated ferritin levels were seen in 89% of these patients, nearly half of whom had levels greater than five times normal (R).
An exaggerated ferritin response with levels above 5 times the normal upper level predicted chronic Still’s disease with 100% accuracy. Ferritin was useful in distinguishing these patients from clinically similar rheumatoid arthritis patients (R).
Ferritin is High in Hemochromatosis
Genetic mutations in the hemochromatosis gene (HFE) make up the most common genetic cause of elevated ferritin levels and are usually seen in patients with northern European ancestors (R).
High ferritin robustly predicts the risk of cirrhosis, the main clinical manifestation of hemochromatosis. Several studies have shown that cirrhosis of the liver rarely occurs in hemochromatosis patients with ferritin levels below that of 1000 micrograms/liter (R).
Ferritin is Extremely High in Hemophagocytic Syndrome
Hemophagocytic syndrome (also known as macrophage activation syndrome or lymphohistiocytic syndrome) is a group of disorders with a final common pathway consisting of elevated triglycerides, elevated ferritin, deficiency of all blood cells, and multiple organ failure. The syndrome is strongly associated with autoimmune disorders, particularly systemic lupus erythematosus and Still’s disease, and viral infections, particularly Epstein-Barr virus (R).
Ferritin in hemophagocytic syndrome is classically elevated above 10,000 ng/L (R).
Diseases Associated With Lower Ferritin
Patients with iron deficiency, as measured by ferritin, have an increased risk of unipolar depressive disorder (OR = 2.34), bipolar disorder (OR = 5.78), anxiety disorder (OR = 2.17), autism spectrum disorder (OR = 3.08), attention deficit hyperactivity disorder (OR = 1.67), tic disorder (OR = 1.70), developmental delay (OR = 2.45), and mental retardation (OR = 2.70) (R).
Low Ferritin Indicates Anemia
Low blood ferritin indicates depletion of iron stores and is a diagnostic criterion for iron deficiency and anemia (R).
Anaemia can manifest as fatigue, headache, dizziness, shortness of breath, or elevated heart rate (tachycardia), and generally lowers the overall quality of life. Motility disorder, nausea, anorexia, and even malabsorption have also been attributed to this condition (R).
A common finding in anemia is irregularity or absence of menstrual periods in women, while men may suffer from impotence. Loss of libido may contribute to impaired quality of life in both sexes (R).
Several studies have confirmed that treatment of anaemia improves cognitive function. That is because iron is a component of many essential enzymes, and therefore iron deficiency alone may impair cognitive function. Indeed, correction of iron-deficiency in non-anaemic girls was shown to improve verbal learning and memory (R).
Low Ferritin is Associated With Fatigue
Ferritin and iron depletion can be found in some fatigue patients.
Intravenous administration of iron improved fatigue in iron-deficient, nonanemic women (R). Over 80 percent had reduced fatigue after receiving iron.
A couple of studies recommend iron supplementation for women with unexplained fatigue who have ferritin levels below 50 μg/L (R).
Ferritin is Lower in Fibromyalgia
The average serum ferritin levels in the fibromyalgia 27.3 and 43.8 ng/ml in a healthy group.
Statistical analyses shows that ferritin levels below 50 ng/ml caused a 6.5-fold increased risk for Fibromyalgia.
Ferritin is Lower in IBD
In fact, anemia is a common complication associated with inflammatory bowel disease (IBD). The World Health Organization estimates that more than 30% of the population have iron deficiency anemia yet it remains an under-managed feature of many gastrointestinal conditions. Also, one third of inflammatory bowel disease (IBD) patients suffer from recurrent anemia (R).
Almost every anemic patient with IBD demonstrates some degree of iron deficiency as a consequence of dietary restrictions, malabsorption, or intestinal bleeding (R).
Both iron deficiency and anaemia of chronic disease (ACD) contribute to the development of anaemia in IBD (R).
Inflammation and ACD is why anemic IBD patients can have elevated ferritin. CRP can be used to exclude inflammation.
Chronic fatigue, a frequent IBD symptom itself, is commonly caused by anemia and may debilitate patients as much as abdominal pain or diarrhea (R).
In IBD, oral iron treatment is limited by poor absorption, intolerance, and induction of oxidative stress at the site of bowel inflammation. However, intravenous iron sucrose has a good safety profile and a 65–75% response rate within 4–8 weeks, which is paralleled by improvement in the quality of life. Additionally, combination therapy with erythropoietin (Epo) leads to a faster and larger hemoglobin increase (R).
When anemic Crohn’s disease patients were treated with iron sucrose and Epo, the feeling of well being, mood, physical ability, and social activities improved. Also, individual patients reported relief of disturbed sleep and increased appetite or libido (R).
Iron deficiency may enhance the IFNgamma response in Th1 driven inflammation in immune mediated inflammatory disorders such as Crohn’s disease (R).
Ferritin is Lower in Hypothyroidism
Alterations in thyroid status and activity result in changes in blood ferritin levels (R).
Ferritin is Lower in Depression and Anxiety
In another study, patients with iron deficiency, as measured by ferritin, have an increased risk of unipolar depressive disorder (OR = 2.34), bipolar disorder (OR = 5.78) and anxiety disorder (OR = 2.17) (R).
Low Ferritin Causes ADHD
Iron deficiency has been associated with attention and behavioral problems and ADHD.
Children who were on ADHD meds showed a stronger association between ferritin and ADHD symptom severity (R).
These findings add to the growing literature implicating iron deficiency in ADHD (R).
Iron supplementation should be investigated as a potential intervention in individuals with low iron stores and ADHD (R).
Ferritin in Neurodegenerative Diseases
Several iron disorders that affect movement and other neurologic functions (Parkinson’s disease and restless legs syndrome) are linked to abnormalities in ferritin (R).
It could be that lower ferritin in the cell may contribute to these disorders by causing higher levels of free iron. This may or may not be related to blood ferritin.
A rare genetic disease, neuroferritinopathy, is a result of mutations in the gene encoding a component of ferritin. It is thought that the mutations impair ferritin assembly lead to a loss of iron storage capacity within brain cells, which causes iron-mediated cell injury (R).
Mitochondrial ferritin (FtMt) has a protective role in neurodegenerative diseases (R,R). Mitochondrial ferritin lowers reactive oxygen species (ROS) accumulation and reduces cell damage in Parkinson’s and Alzheimer’s disease in animal models (R).
Ferritin is Lower in Celiac Disease
Ferritin in Restless Legs Syndrome
Restless Legs Syndrome is a neurologic disorder characterized by unpleasant sensations in the legs that appear mostly at night upon retiring, including an irrepressible urge to move the limbs (R).
It was suggested that patients with restless legs syndrome have lower ferritin levels in spinal fluid and parts of the brain (R).
Factors that Elevate Ferritin
In normal subjects, daily iron loss amounts to 1–2 mg and this requires a similar amount of iron to be taken up from the diet (R).
Menstruating women lose more blood than their male counterparts and are therefore at higher risk of iron deficiency (R).
1) Iron Supplements
Supplementing with 30 mg/d of iron for 90 days increased ferritin concentration in schoolchildren with low iron stores, and this effect persisted 6 months after supplementation (R).
Oral iron supplements commonly contain iron in the form of ferrous salts (ferrous sulphate, ferrous gluconate, and ferrous fumarate). All ferrous compounds are oxidized in the gut, releasing reactive radicals as byproducts. These will attack the gut wall and produce a range of gastrointestinal symptoms and discomfort (R). This problem is especially pronounced in IBD patients where oral iron may enhance gut inflammation (R).
Another good alternative is intravenous iron supplementation (R).
2) Iron-rich Foods
- Dietary iron occurs in two forms: heme (from meat, poultry, and fish) and non-heme (mostly from plants) (R).
- Non-heme iron absorption depends on many factors, including the presence of stomach acid and Vitamin C. Inhibitors such as phytic acid and polyphenols (in vegetables) reduce non-heme absorption (R).
- Heme iron is released after mechanical and enzymatic digestion of myoglobin found in meat and fish (R).
Consuming iron-rich foods improves iron stores and ferritin levels. These include green leafy vegetables, cocoa powder and dark chocolate, oatmeal, cereals, wheat germ, beans and tofu, lamb and beef, nuts, pumpkin and squash seeds, liver and mollusks, etc.
Red meat consumption correlates significantly with ferritin in the blood (R).
3) Vitamin C
Alcohol enhances the absorption of iron.
Alcohol consumption is significantly associated with levels of ferritin (R).
There was a positive relationship between wine intake and concentrations of both ferritin and iron in the blood (R).
In alcohol abuse, ferritin levels are elevated and rapidly decrease with alcohol abstinence (R).
Women who smoke have higher ferritin and higher body iron compared to nonsmoking women. However, when women smoke during pregnancy, their newborn infants have lower iron stores than those of non-smoking mothers (R).
Tobacco smoking was associated with elevated ferritin concentrations in Parkinson’s disease patients (in this setting smoking had a beneficial effect) (R).
6) Proinflammatory Cytokines
Pro-inflammatory cytokines stimulate the production of ferritin, which in inflammation/infection acts as an acute phase reactant (R).
Factors that Decrease Ferritin
Because there is no excretory route, iron level is regulated by iron uptake. If iron absorption is not tightly regulated, iron overload and associated toxicity occur (R).
1) Dairy Products
Calcium-rich foods, such as dairy products, may decrease the absorption of iron.
Pregnant women who had consumed cow’s milk at least 3 times a week had lower levels of ferritin and body iron (R).
A diet rich in milk and yogurt increased the risk of low iron status by 50 percent in women in New Zealand (R).
Coffee interferes with the utilization of supplemental iron (R).
Tea contains tannins which inhibit the absorption of iron. However, tea does not seem to impact ferritin levels in healthy adults. It may only lower ferritin in those with iron deficiency or iron overload.
Fiber impairs the absorption of iron.
Intake of fiber-poor fruits, vegetables, and juices were associated with higher ferritin concentrations in premenopausal women (R).
Regular physical activity, especially extensive running, increases iron loss. Mild iron deficiency (abnormal blood ferritin and normal hemoglobin concentration) and sometimes true iron deficiency anemia can occur especially when nutritional iron intake is insufficient and iron demand is increased because of growth (children, adolescents) or additional iron loss (by menstruation) (R).
Iron deficiency is common in athletes involved in endurance sports. In female marathon runners, the prevalence is as high as 28%, compared to 11% in the general female population (R).
Endurance athletes need more iron because their training causes an expansion in the amount of red blood cells. This means that their hemoglobin levels may seem normal but their ferritin levels (a marker of the iron reserves stored in the body) may be low.
Low ferritin with hemoglobin in the mid- to upper normal range, and low ferritin with hemoglobin in the low normal range are relative indications for iron supplementation in athletes (R).
6) Blood Donation
Ferritin levels are lowered after donating blood.
Decrease in ferritin is dependent both on the number of blood donations as well as the periodicity between them (R).
7) Estrogen and Progestin Hormone Therapy
Estrogen may lower ferritin.
Longer times since menopause and longer times since the last hormone use were associated with higher ferritin concentrations (R).
This effect of aspirin on ferritin was more marked in diseased subjects with inflammation, infection or liver disease (R).
Risedronate treatment is associated with significantly decreased ferritin levels in postmenopausal women with osteoporosis and cardiovascular risk factors (R).
Recommended Supplements for Increasing Ferritin/Iron Status Without Gut Problems
This post was cowritten by Joe and researcher with a PhD in Biology.