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.
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 .
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 .
Mice deficient in ferritin die in the embryo stage .
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 .
Mitochondrial ferritin (FtMt) is produced by specific tissues, such as the testis and the brain .
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 .
The liver’s stores of ferritin are the primary source of reserve iron in the body .
As previously mentioned, ferritin plays an important role in the storage of cellular iron .
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 .
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 .
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 .
Ferritin acts as a buffer against iron deficiency and iron overload .
Additionally, it was shown that circulating ferritin may assume roles entirely independent of its classic role as an iron-binding protein .
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 .
One study suggests that blood ferritin actually originates from damaged cells, which reflects cellular damage .
Ferritin can modulate immune function by inhibiting lymphocyte function. Ferritin decreased the number of granulocyte-macrophages and red blood cell precursors in mice .
Ferritin also suppressed immune activity in humans .
Ferritin can stimulate blood vessel growth in inflammation and is desirable in wound healing, but undesirable in tumors .
Unless indicated otherwise, the statements in the text below refer to the circulating ferritin found in blood.
Normal Reference Ranges for Ferritin (Serum)
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 .
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 .
Reference Range for Ferritin 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 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 .
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.
High Ferritin Levels
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) .
Ferritin, in turn, can increase the liver proinflammatory mediators IL-1b, iNOS, RANTES, IkappaBα, and ICAM1 .
Ferritin is used as an indicator of iron overload disorders, such as hemochromatosis or hemosiderosis.
As ferritin is also an acute-phase reactant (a part of the 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 1,000 ng/ml are a nonspecific marker of illness, including infections and cancer .
However, ferritin over 300 can indicate some inflammation.
Diseases Associated with Higher Ferritin
The most common causes of elevated ferritin levels are obesity, inflammation, and daily alcohol intake. The most common causes of genetic-related elevated ferritin levels is the condition hemochromatosis. Additional causes include diabetes and metabolic syndrome [15, 16].
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 .
The elevated ferritin in these states reflects increased total body iron stores, 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) .
Note that although ferritin levels generally increase in infection, some infections also result in decreased ferritin .
- Inflammatory conditions 
- Chronic kidney disease 
- Rheumatoid arthritis 
- Autoimmune disorders 
- Acute infections 
- Cancer [5, 5, 5]
- Anemia of Chronic Disease 
- Type 2 diabetes 
- Metabolic syndrome 
- Atherosclerosis 
- Fatty liver disease 
- Anorexia 
- Graves’ disease 
- Arrhythmias 
- Chronic Hepatitis C infection 
- Hemochromatosis 
- Hemophagocytic syndrome 
- Still’s disease 
- Sideroblastic anemia 
Potential Causes of Higher Ferritin
High ferritin levels can point to many health conditions, some of which are listed below. If your ferritin is high, talk to your physician as soon as possible. He or she should diagnose and treat the underlying condition that may be increasing your ferritin levels.
Ferritin is used as an indicator of iron overload disorders, such as hemochromatosis or hemosiderosis.
A number of conditions can cause iron overload, including:
- Rheumatoid arthritis
- Metabolic syndrome
- Type 2 diabetes
- Other inflammatory diseases
- Iron poisoning
- Cancer, such as leukemia, lymphoma, or breast carcinoma
- Liver disease
- Recent blood transfusion
Additionally, pro-inflammatory cytokines stimulate the production of ferritin, which, in relation to inflammation/infection, acts as an acute phase reactant .
Alcohol enhances the absorption of iron. Alcohol consumption is significantly associated with high ferritin levels .
There was a positive relationship between wine intake and concentrations of both ferritin and iron in the blood .
In alcohol abuse, ferritin levels are elevated and rapidly decrease with alcohol abstinence .
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 .
Tobacco smoking was associated with elevated ferritin concentrations in Parkinson’s disease patients (in this setting smoking had a beneficial effect) .
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 .
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 .
Vegetarians can have significantly lower blood ferritin levels, resulting from iron deficiency. One study found 19% of vegetarians have iron deficeintcy .
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:
- Unexplained fatigue
- Hair loss
- IBD and/or celiac disease
- Attention issues/ADHD
- Parkinson’s and/or restless leg syndrome
- Chronic headaches
- Unexplained weakness
- Ringing in the ears
- Leg pains
- Shortness of breath
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 .
- Anemia 
- Fatigue 
- Hair loss [34, 35, 36, 37]
- Fibromyalgia 
- IBD 
- Hypothyroidism 
- Depression 
- Anxiety 
- ADHD 
- Celiac disease [42, 43]
- Parkinson’s 
- Restless leg syndrome 
Ferritin and iron depletion are found in some fatigue patients.
Intravenous administration of iron improved fatigue in iron-deficient, nonanemic women .
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 .
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 .
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 .
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 .
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 .
High iron load lowers inflammation by decreasing inflammatory cytokines such as TNF-a and lowering Th1 and increasing Th2 function .
Alterations in thyroid status and activity resulted in changes in blood ferritin levels .
Blood ferritin levels increased in hypothyroid patients with Hashimoto’s disease when normal thyroid function was achieved with L-Thyroxine therapy .
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 .
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 .
The study implies a possible association between depression and decreased ferritin level before the occurrence of anemia .
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) .
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.
Iron is associated with dopamine metabolism, and low iron levels might be associated with more significant impairment in dopamine function in subjects with 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 .
These findings add to the growing literature implicating iron deficiency in ADHD .
In women without systemic inflammation or other underlying disorders, ferritin levels below or equal to 30 ng/mL are strongly associated with hair loss .
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 .
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) .
Certain drugs have been linked with lower ferritin levels. Discuss your medications with your physician.
Subjects who took >7 aspirins/week had significantly lower ferritin than nonusers, who took <1 aspirin/week .
This effect of aspirin on ferritin was more marked in diseased subjects with inflammation, infection, or liver disease .
Estrogen and Progestin Hormone Therapy
Longer times since menopause and longer times since the last hormone use were associated with higher ferritin concentrations .
Risedronate treatment is associated with significantly decreased ferritin levels in postmenopausal women with osteoporosis and cardiovascular risk factors .
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 .
Menstruating women lose more blood than their male counterparts and are therefore at higher risk of iron deficiency .
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 .
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 .
This problem is especially pronounced in IBD patients where oral iron may enhance gut inflammation .
Ferric iron polymaltose complex or heme iron polypeptide are also available and may present safer and better-tolerated alternatives .
Intravenous iron supplementation under medical guidance is another strategy .
- Ferric iron polymaltose complex + heme iron polypeptide 
- Lactoferrin – formulas with infants fed lactoferrin had higher ferritin levels [51, 52]
Do not take iron supplements before consulting a physician.
- Dietary iron occurs in 2 forms: Heme (from meat, poultry, and fish) and non-heme (mostly from plants) .
- 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 .
- Heme iron is released after mechanical and enzymatic digestion of myoglobin found in meat and fish .
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 .
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 .
In one experiment, beef protein enhanced iron absorption 80% better than did chicken protein.
Chicken, salmon, and pork also increase iron absorption.
2) Vitamin C
Ascorbic acid uptake induces both iron-independent and iron-dependent ferritin production .
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 .
There are some confounding variables in some of the studies, however.
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 .
Studies show that sugar, especially fructose, increases iron bioavailability .
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 .
L-alanine increases ferritin .
A copper deficiency can reduce iron absorption in rats .
Ways to Decrease Ferritin
It’s important to speak with your doctor if your ferritin is high. Your doctor should diagnose and treat any underlying conditions causing your high ferritin levels.
You may try the additional strategies listed below if you and your doctor determine that they could be appropriate for lowering your iron. Discuss the strategies listed here with your doctor. Remember that none of them should ever be done in place of what your doctor recommends or prescribes.
1) Hemochromatosis Diet (Foods Low in Iron)
Hemochromatosis is a common cause of high ferritin. People with this condition absorb too much iron from food, which excessively raises blood iron levels.
Generally, the optimal diet for people with hemochromatosis is low in iron.
Additionally, various factors can affect the amount of iron people absorb, such as:
- Dietary iron forms: heme (from meat, poultry, and fish) vs. non-heme (mostly from plants) iron. Hem iron is absorbed better .
- Stomach acid and vitamin C, which increase non-heme iron absorption .
- Phytic acid and polyphenols (in vegetables), which reduce non-heme absorption .
Having these factors in mind, in addition to lowering the intake of iron-rich foods, additionally affects iron balance and absorption in the body.
For example, you can and should still eat green, leafy vegetables, as they only contain non-heme iron. This type of iron is much harder to absorb.
Many fresh vegetables also contain polyphenols, which act as antioxidants and lower iron absorption.
You can also consume more legumes and grains, which contain compounds that reduce iron absorption (phytic acid). The ways in which you may modify a healthy hemochromatosis diet is explained in more detail below.
2) Green Tea & Coffee
Both tea and coffee contain tannins and polyphenols, 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.
Ferritin concentrations were not related to black, green, or herbal tea consumption in healthy adults .
However, ferritin displayed a negative correlation with the consumption of tea in the elderly .
Tea consumption was associated with lower ferritin in groups with a high prevalence of iron deficiency .
In those at risk for iron overload, tea consumption may lower ferritin concentrations .
Additionally, coffee interferes with the utilization of supplemental iron .
Fiber impairs the absorption of iron.
Intake of fiber-poor fruits, vegetables, and juices was associated with higher ferritin concentrations in premenopausal women .
4) Whole Grains (Phytic Acid)
Phytic acid is common in pretty much all plant-based foods, including whole grains, beans, nuts, and seeds.
Phytic acid is a potent inhibitor of native and fortification iron absorption .
In people, there is a dose-dependent inhibitory effect of phytate on iron absorption .
Iron absorption increased four- to fivefold in humans when phytic acid was reduced from its normal amount in soy .
On the other hand, long-term, routine exercise lowers ferritin along with other acute phase reactants .
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) .
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 .
Endurance athletes need more iron because their training causes an expansion in the number 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 .
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 .
A diet rich in milk and yogurt increased the risk of low iron status by 50% in women in New Zealand .
However, although some short-term effects have been observed, long-term calcium supplementation was not observed to negatively impact iron status and ferritin concentration .
Zinc is an essential mineral commonly found in multi-mineral supplements. Zinc is important for immune function.
Zinc may interfere with iron absorption because of similar chemical properties and shared absorption pathways.
In human trials, zinc supplementation alone does not appear to have a clinically important negative effect on iron status. However, when zinc is given with iron, iron indicators do not improve as greatly as when iron is given alone .
Manganese is an essential mineral commonly found in multi-mineral supplements.
Manganese may interfere with iron absorption because of similar chemical properties and shared absorption pathways.
In humans, manganese inhibited iron absorption dose-dependently both in solutions and in a hamburger meal. Manganese has a strong direct competitive inhibition of iron absorption .
Some types of common magnesium supplements, such as magnesium oxide, can impair iron absorption in cellular studies .
It can also help rats with iron overload .
In a model of borderline iron deficiency, rats fed curcumin had an induced full-blown deficiency .
11, 12, & 13) Peppermint, Cocoa, and Chamomile
Compared with humans who just drank water :
- Beverages containing 20 to 50 mg total polyphenols/serving reduced iron absorption from the bread meal by 50 to 70%
- Beverages containing 100 to 400 mg total polyphenols/serving reduced iron absorption by 60 to 90%
Inhibition of iron by teas (same concentration of polyphenols) :
- Black tea = 79 to 94%
- Peppermint tea = 84%
- Pennyroyal = 73%
- Cocoa = 71%
- Vervain = 59%
- Lime flower = 52%
- Chamomile = 47%
Egg yolks decrease the absorption of iron .
15) Grapeseed Extract (and Anthocyanins)
Regular consumption of dietary vitamin C can easily counteract the inhibitory effects of low concentrations of dietary polyphenols on heme iron absorption, but cannot counteract the inhibitory actions of high concentrations of polyphenols .
Chili is capable of inhibiting iron absorption in a study performed on young women .
Low Ferritin Levels?
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