Ferritin stores iron and transports it to where it is required. In blood, it is a key indicator of total iron stores. Find out why it is important to keep this protein in balance and which factors increase ferritin levels.
What Is Ferritin?
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 transports it to areas where it is required [1].
Although iron plays many important roles in the body, it can also 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 [1].
Mice deficient in ferritin die in the embryo stage [1].
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 [2].
Mitochondrial ferritin (FtMt) is produced by specific tissues, such as the testis and the brain [3].
Small amounts of ferritin are also secreted into the blood, functioning as an iron carrier. Apart from the blood, ferritin is also secreted into joint (synovial) and spinal fluids [2].
The liver’s stores of ferritin are the primary source of reserve iron in the body [4].
Ferritin Roles/Functions
As previously mentioned, ferritin plays an important role in the storage of cellular iron [5].
It functions in cell detoxification, limiting the formation of reactive oxygen species, and mitigating their damaging effect on cellular structures [6].
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 [6].
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 4,500 iron atoms [5].
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 [5].
Ferritin acts as a buffer against iron deficiency and iron overload [7].
Additionally, it was shown that circulating ferritin may assume roles entirely independent of its classic role as an iron-binding protein [5].
Ferritin may play an important role in skin defense. Ferritin in the skin is increased by UVA and infrared-A radiation. Increased ferritin following acute UV/IR radiation offers increased protection against subsequent oxidative stress [8, 9].
Ferritin is an acute phase reactant and a marker of acute and chronic inflammation. It is nonspecifically elevated in a wide range of inflammatory conditions [5].
One study suggests that blood ferritin actually originates from damaged cells, which reflects cellular damage [10].
Ferritin can behave as a real pro-inflammatory cytokine, activating the NFκB cascade and inducing liver damage [11].
Ferritin can modulate immune function by inhibiting lymphocyte function. Ferritin decreased the number of granulocyte-macrophages and red blood cell precursors in mice [5].
Ferritin also suppressed immune activity in humans [5].
Ferritin can stimulate blood vessel growth in inflammation and is desirable in wound healing, but undesirable in tumors [5].
Unless indicated otherwise, the statements in the text below refer to the circulating ferritin found in blood.
Ferritin Blood Test
Why It’s Important
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 [5].
Ferritin is normally high at birth. Ferritin levels rise during the first 2 months of age and then fall until the end of the first year of life and later infancy. Around 1 year of age, ferritin levels begin to rise again [12].
Normal Ferritin Levels (Serum)
- 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 to 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 to 200 ng/ml for women [5].
However, ferritin ranges for optimal health are different than the normal ranges.
Note that ferritin increases in response to stressors, 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.
Some lab-to-lab variability occurs due to differences in equipment, techniques, and chemicals used. Don’t panic if your result is slightly out of range – as long as it’s in the normal range based on the laboratory that did the testing, your value is normal.
However, it’s important to remember that a normal test doesn’t mean a particular medical condition is absent. Your doctor will interpret your results in conjunction with your medical history and other test results.
Have in mind that a single test isn’t enough to make a diagnosis. Your doctor will interpret this test, taking into account your medical history and other tests. A result that is slightly outside the normal range may not be of medical significance, as this test often varies from day to day and from person to person.
Low Ferritin Levels (Ferritin Deficiency)
Range
Blood ferritin anywhere below 12 to 30 ng/ml indicates depletion of iron stores and is a diagnostic criterion for iron deficiency [5, 13].
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 [14].
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, and 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 [5].
Other than anemia, low ferritin may also indicate hypothyroidism, vitamin C deficiency, or celiac disease [5, 15].
Vegetarians can have significantly lower blood ferritin levels, resulting from iron deficiency. One study found 19% of vegetarians have iron deficeintcy [16].
Symptoms of Low Ferritin (Serum)
Your doctor may order a ferritin test if you have some of the following symptoms associated with low ferritin levels:
- Anemia
- Unexplained fatigue
- Hair loss
- IBD and/or celiac disease
- Fibromyalgia
- Depression
- Anxiety
- Hypothyroidism
- Attention issues/ADHD
- Parkinson’s and/or restless leg syndrome
- Dizziness
- Chronic headaches
- Unexplained weakness
- Ringing in the ears
- Irritability
- Leg pains
- Shortness of breath
Symptoms of low ferritin depend on the underlying cause, which is why it’s so important to see a doctor and get adequate diagnosis and treatment if you experience any of the symptoms mentioned above.
Diseases Associated with Lower Ferritin
Iron-Deficiency Anemia & Other
Low ferritin may signal iron-deficiency anemia.
Lower ferritin levels may also be caused by certain medications such as antacids (reduce iron absorption) and nonsteroidal anti-inflammatory medicines (may can cause blood loss in the digestive tract).
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). One paper also found a link between iron deficiency and mental retardation (OR = 2.70), which remains unconfirmed [17].
- Anemia [5]
- Fatigue [18]
- Hair loss [19, 20, 21, 22]
- Fibromyalgia [23]
- IBD [24]
- Hypothyroidism [25]
- Depression [26]
- Anxiety [17]
- ADHD [27]
- Celiac disease [28, 29]
- Parkinson’s [1]
- Restless leg syndrome [1]
Fatigue
Ferritin and iron depletion are found in some fatigue patients.
Intravenous administration of iron improved fatigue in iron-deficient, nonanemic women [18].
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 [30].
One study suggested a possible, yet weak and unproven, link between low ferritin and symptoms of fibromyalgia. In the study, the average serum ferritin levels in the fibromyalgia group were 27.3, and 43.8 ng/ml in healthy controls. Further studies are needed to determine if a link between fibromyalgia and low ferritin exists [23].
IBD
Chronic intestinal bleeding in inflammatory bowel disease (IBD) may exceed the amount of iron that can be absorbed from the diet, resulting in a negative iron balance. Thus, IBD most likely lowers iron [24].
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 undermanaged feature of many gastrointestinal conditions. Also, one-third of inflammatory bowel disease (IBD) patients suffer from recurrent anemia [24].
Almost every anemic patient with IBD demonstrates some degree of iron deficiency as a consequence of dietary restrictions, malabsorption, or intestinal bleeding.
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 from disturbed sleep and increased appetite or libido [24].
Iron deficiency may enhance the inflammatory IFN-gamma response in Th1 driven inflammatory disorders such as Crohn’s disease [24].
High iron load lowers inflammation by decreasing inflammatory cytokines such as TNF-a and lowering Th1 and increasing Th2 function [24].
Hypothyroidism
Alterations in thyroid status and activity resulted in changes in blood ferritin levels [31].
Subclinical hypothyroidism is associated with iron-deficiency anemia and lower ferritin levels [25, 32].
Blood ferritin levels increased in hypothyroid patients with Hashimoto’s disease when normal thyroid function was achieved with L-Thyroxine therapy [31].
In patients with Graves’ disease (higher thyroid hormones), ferritin is higher and decreases back to normal when normal thyroid function is achieved by antithyroid drug therapy [31].
Depression & Anxiety
The average ferritin level in students with depression was significantly lower than healthy ones. In the study, low ferritin increased the odds of depression by 1.92X [26].
The study implies a possible association between depression and decreased ferritin level before the occurrence of anemia [26].
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) [17].
The mechanism could be related to lower dopamine and serotonin in iron deficiency, but large-scale studies are needed to shed light on this link.
ADHD
Iron is associated with dopamine metabolism, and low iron levels might be associated with more significant impairment in dopamine function in subjects with ADHD [27].
Iron deficiency has been associated with attention and behavioral problems and ADHD.
Kids with lower ferritin (average of 18.4 ng/mL) had worse inattention, hyperactivity/impulsivity, and ADHD symptoms [33, 27, 17].
Children who were on ADHD meds showed a stronger association between ferritin and ADHD symptom severity [33].
These findings add to the growing literature implicating iron deficiency in ADHD [33].
Hair Loss
Multiple studies have found low ferritin correlating with hair loss [19, 20, 21, 22].
In women without systemic inflammation or other underlying disorders, ferritin levels below or equal to 30 ng/mL are strongly associated with hair loss [21].
A total of 210 patients with male and female pattern hair loss were compared to 210 healthy controls. Ferritin concentration was lower in patients with female pattern hair loss (49.27 ng/ml), compared with normal healthy women (77.89 ng/ml).
Among male patients, 22.7% of them showed lower ferritin than 70 ng/ml, while none of the men without hair loss had lower than 70 ng/mL [22].
The average ferritin level in patients with male pattern baldness (37.3 ng/ml) and an autoimmune hair loss disease called alopecia areata (24.9) was statistically significantly lower than in people without hair loss (59.5) [20].
Medications
Medication-Related
Certain drugs have been linked with lower ferritin levels. Discuss your medications with your physician.
Aspirin
Subjects who took >7 aspirins/week had significantly lower ferritin than nonusers, who took <1 aspirin/week [34].
This effect of aspirin on ferritin was more marked in diseased subjects with inflammation, infection, or liver disease [34].
Estrogen and Progestin Hormone Therapy
Current users of oral conjugated estrogen plus progestin had significantly lower ferritin concentrations than did current users only taking estrogen [35].
Longer times since menopause and longer times since the last hormone use were associated with higher ferritin concentrations [35].
Other
Risedronate treatment is associated with significantly decreased ferritin levels in postmenopausal women with osteoporosis and cardiovascular risk factors [36].
Ways to Increase Ferritin Levels
Most importantly, work with your doctor to treat any underlying conditions causing your low ferritin levels.
You may try the additional strategies listed below if you and your doctor determine that they could be appropriate for increasing your iron levels. None of these strategies should ever be done in place of what your doctor recommends or prescribes.
1) Iron Intake
In normal subjects, the daily iron loss amounts to 1 to 2 mg, and this requires a similar amount of iron to be taken up from the diet [24].
Menstruating women lose more blood than their male counterparts and are therefore at higher risk of iron deficiency [24].
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 [37].
Oral iron supplements commonly contain iron in the form of ferrous salts (ferrous sulfate, 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 [24].
This problem is especially pronounced in IBD patients where oral iron may enhance gut inflammation [24].
Ferric iron polymaltose complex or heme iron polypeptide are also available and may present safer and better-tolerated alternatives [24].
Intravenous iron supplementation under medical guidance is another strategy [24].
Recommended:
- Ferric iron polymaltose complex + heme iron polypeptide [24]
- Lactoferrin – formulas with infants fed lactoferrin had higher ferritin levels [38, 39]
Do not take iron supplements before consulting a physician.
Iron-Rich Foods
- Dietary iron occurs in 2 forms: Heme (from meat, poultry, and fish) and non-heme (mostly from plants) [24].
- 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 [24].
- Heme iron is released after mechanical and enzymatic digestion of myoglobin found in meat and fish [24].
Consuming iron-rich foods improves iron stores and ferritin levels. These include green leafy vegetables, cocoa powder, dark chocolate, oatmeal, cereals, wheat germ, beans and tofu, lamb and beef, nuts, pumpkin and squash seeds, liver and mollusks, among others.
Red meat consumption correlates significantly with ferritin in the blood [40].
Meat is not only a source of iron itself, but it can help you absorb non-heme iron from plant-based foods 57% better from a 75 g portion [41].
In one experiment, beef protein enhanced iron absorption 80% better than did chicken protein.
The increased absorption of iron come from the protein and fat in meat [42, 43].
Chicken, salmon, and pork also increase iron absorption.
2) Vitamin C
Vitamin C (ascorbic acid) increases the bioavailability of iron and its absorption from dietary sources [44].
Ascorbic acid uptake induces both iron-independent and iron-dependent ferritin production [45].
3) Vitamin A and Beta-Carotene
In multiple human studies, simultaneous use of iron and vitamin A supplements seemed to be more effective to prevent iron deficiency anemia than the use of these nutrients alone [46].
There are some confounding variables in some of the studies, however.
Beta-carotene significantly increases the absorption of iron. In the presence of phytates, polyphenols, or tannins, beta-carotene generally overcame the inhibitory effects in humans [47, 48].
Other
Evidence that simple sugars such as glucose and fructose affect iron bioavailability first arose in the 1960s from work showing that sugars were able to form stable, soluble complexes [49].
Studies show that sugar, especially fructose, increases iron bioavailability [49].
Consuming iron with fruit might be a good idea.
Adding 1 g of citric acid to a meal containing 3 or more mg of iron could help iron absorption [50].
L-alanine increases ferritin [51].
A copper deficiency can reduce iron absorption in rats [52].
Takeaway
Ferritin is a protein that stores and transports iron in the blood. It helps detox cells by reducing oxidative stress and works as a buffer against iron deficiency and iron overload.
Low ferritin can signal anemia, hypothyroidism, vitamin C deficiency, celiac disease, and many other conditions.
Symptoms may include anemia, fatigue, mood changes, and many others. These symptoms depend on the underlying cause of low ferritin levels, which needs to be diagnosed and treated by a doctor.
Complementary approaches that may help increase ferritin levels can include increasing dietary iron intake (particularly with heme-rich animal sources) and vitamin C.
