Iron is essential for many vital processes. When people go to their doctor to get their iron tested, almost always, the results are not scrutinized, even though we know that you can be healthier and live longer when your results lie within optimal ranges.
Iron deficiency can lead to anemia and several health problems. Read this post to learn about the negative health effects of iron deficiency.
This post is part 2 of a 4 Part Series
Part 1: Iron Metabolism, Lab Tests, Iron Deficiency Anemia and Overload
Part 2: 47 Negative Health Effects of Iron Deficiency
Part 3: Iron Intake and Ways to Increase or Decrease Iron
Part 4: Negative Health Effects of High Iron
Negative Health Effects of Iron Deficiency
Iron Deficiency is Linked to Poor Cognitive Development in Children
In terms of brain development and brain health in infants and children, iron is critical for:
- brain and neurological development [1].
- normal functioning of the brain [1].
- neurotransmitter production (dopamine and noradrenaline)
- myelination of nerve cells
- immune function in the brain
- hippocampal structure and function [2, 3, 4].
1) Attention Deficit Hyperactivity Disorder
Lower iron and ferritin levels are associated with increased hyperactivity in children with ADHD [5, 6]. Blood ferritin levels were low (<30 ng/mL) in 84% of the children with ADHD as compared to 18% of healthy children [7, 8, 9]. Children with ADHD also have lower blood levels of iron and ferritin [10].
In addition, among ADHD patients, low blood ferritin levels were associated with the severity of ADHD symptoms and cognitive deficiency [11, 10].
Patients with iron deficiency anemia also report an increased risk of ADHD [12, 13].
Low brain iron stores may contribute to ADHD symptoms because low iron levels in the brain can alter the activity of dopamine, a neurotransmitter involved in movement, cognitive functions, and attention [11].
Treatment with iron supplements can be an effective alternative to treat patients with ADHD and iron deficiency [14, 11].
Iron supplementation (80 mg/day) improves ADHD symptoms in children with low blood ferritin levels [15, 16, 8].
Low iron level in the brain is a promising marker of ADHD [6, 17] as children with ADHD have lower iron in the thalamus [6]. However, other studies did not detect low ferritin in children with ADHD, suggesting that blood iron measures may not provide reliable markers for ADHD [17, 18, 19, 20].
2) Autism
Iron deficiency and anemia are prevalent among autistic children [21, 22, 12]. Iron deficiency may contribute to learning and behavioral impairments observed in children with autism spectrum disorder (ASD)
Iron deficiency may contribute to learning and behavioral impairments observed in children with autism spectrum disorder (ASD) [23]. The risk for ASD increases with lower maternal iron intake
The risk for ASD increases with lower maternal iron intake [24]. However, not all autistic children have low iron
However, not all autistic children have low iron [25].
3) Causes Mental Retardation and Delayed Development
Mental retardation and delayed development are more prevalent with iron deficiency anemia in children [26, 27, 12].
Iron deficiency causes poor cognitive, social, and behavioral development [28, 29].
Iron deficiency anemia in infants is also associated with [30, 31, 32, 33]:
- mild or moderate mental retardation [34, 35, 12]
- slower brain development
- poorer school performance later in childhood [30]
- lower scores on language, movement measures, and environmental sound perception [36, 26, 27].
- lower IQ
- poorer attention and memory
- slower language and motor development
Children with iron deficiency anemia are more than twice as likely to score below average on standardized tests than children with normal iron status [37].
Iron Deficiency and Cognitive/Mental Health in Adults
4) Associated with Depression/Anxiety
Severe chronic iron deficiency in infancy is associated with a higher prevalence of anxiety, depression, and attention problems later in life [27].
Iron deficiency can cause abnormal dopaminergic neurotransmission and depress dopaminergic activity.
Weaning rats fed an iron-deficient diet showed decreased physical activity and increased anxiety-like behavior with a reduction of brain dopamine receptors [38].
Both men and women with iron deficiency anemia have a markedly higher risk of developing an anxiety disorder [12].
5) Iron is Lower in Bipolar Disorder
Iron deficiency can cause mood swings, a key factor in the disease progression of bipolar disorder [27, 39, 40, 41].
There is a higher percentage of bipolar disorder among patients with iron deficiency anemia [42].
6) Low Iron is Associated with Tic Disorder
Females with iron deficiency anemia have a significantly increased risk of tic disorder [43].
Ferritin and blood iron levels were markedly lower in Tourette’s syndrome patients, indicating that lower iron availability may have a causal role in the progression of tics and other movement disorders [44].
Iron and Women’s Health
Women of reproductive age are at particular risk of iron deficiency [45].
Data from the National Health and Nutrition Examination Survey indicated that 12 – 16% of nonpregnant women aged 16 – 49 years have iron deficiency, and 2 – 4% have iron-deficiency anemia [46].
Heavy menstrual bleeding is the most common cause of iron deficiency anemia in the developed world [47].
Other factors that increase the risk of iron deficiency in women include [45, 48, 49]:
- the use of an intrauterine device (IUD)
- a vegetarian diet
- accelerated growth during the teenage years
- dieting
- intensive exercise
Women are at greater risk of experiencing fatigue and exhaustion and are 3 times more likely than men to feel fatigued [50].
7) Increases the Risks of Premenstrual Syndrome (PMS) and Worsens PMS symptoms
A low intake of iron is associated with a higher risk of premenstrual syndrome [51].
PMS Symptoms are more severe in anemic women comparing to non-anemic women [52].
Taking dietary and iron supplements for 2 months reduced PMS symptoms considerably in all women having anemia [52].
Eating a diet that provided about 22 mg of iron every day for 10 years was linked to a 33% decrease in risks of developing premenstrual syndrome [51].
8) Linked to Pregnancy Complications
Anemia occurs in 35 – 75% of pregnancies in developing countries, and in 18% of pregnancies in developed countries [53].
Iron requirements are increased during pregnancy because the mother’s blood volume expands, and the developing fetus and placenta need iron to grow [53].
Iron deficiency is associated with higher maternal and fetal risk of death, premature delivery, and lower birth weight [54, 55, 56].
Iron deficiency anemia doubles the risk of preterm delivery and triples the risk of low birth weight [57, 58, 59].
Severe maternal anemia is associated with growth delays and impaired neurological and mental development in newborns [60, 61, 62].
Apgar (Appearance, Pulse, Grimace, Activity, Respiration) scores, assessing newborn’s health, are significantly higher in infants born to iron-supplemented mothers [63].
Iron deficiency after delivery is associated with an increased risk of postpartum depression, increased prevalence of infections, fatigue, and exhaustion, and lower quality and quantity of breast milk produced [64, 65, 66, 67].
Iron is Important for Immune Function
Iron plays an essential role in the normal development of the immune system and resistance to infection (68, 69).
It is necessary for [70, 71]:
- immune cell production
- cytokine production
- immune response
- the generation of reactive oxygen species required for killing pathogens
9) Compromises Immune Function
Iron deficiency is associated with some reduced function of lymphoid organs (tissues that produce lymphocytes) and immune cells, specifically:
- thymus degeneration, resulting in a decrease of T lymphocytes [72].
- reduced neutrophil activity against bacteria. Myeloperoxidase, an enzyme in neutrophils required for killing bacteria, needs iron to function [73]. Neutrophil function is restored to normal with iron supplementation [74, 69, 75].
- reduced cytokine production, including IFN-gamma, TNF-alpha, IL-6, and IL-8
- reduced macrophage functions because iron accumulation within macrophages allow them to generate reactive oxygen species needed to combat infectious agents and cancer cells [76]
- Th2 dominance and lowered Th1 immune responses, which lowers the ability to fight off viral and bacterial infections [77]. Also, functions and growth of Th1 cells are more sensitive to iron removal than Th2 cells in a cell-based study [78].
Antibody concentrations, production, responses to antigens, and complement levels (also called humoral immunity) are less affected by iron deficiency [79].
While iron deficiency hampers the recovery and morbidity of some infections, it seems to help with other infections [80].
10) Causes Skin Problems and Poor Wound Healing
Iron is essential for healthy skin, hair, and nails. Iron is required for collagen production.
Signs of iron deficiency include pale and itchy skin, skin infections (impetigo, candidiasis), fragile nails, and dry and brittle hair [81].
Severe deficiency results in decreased collagen production, and poor wound healing [82].
Iron plays a role in skin changes seen in sunburn, porphyria cutanea tarda, inflammation, and skin cancer [83, 84, 85, 86].
Iron Deficiency and Autoimmune Diseases
Chronic inflammation from infections and autoimmunity can cause iron deficiency, and anemia from chronic inflammation is the most common type of anemias [87]. When the immune system is fighting off a pathogen, inflammatory cytokines increase iron stores and iron inside of immune cells, while lowering systemic iron in order to reduce the iron available to the pathogen.
Chronic inflammation also reduces iron absorption in the gut [88].
Variants in the iron transporter NRAMP1 (encoded by the SLC11A1 gene) is associated with several autoimmune disorders including rheumatoid arthritis, diabetes and multiple sclerosis [89, 90, 91].
Also, iron can increase the production of several autoantigens initiating the process of autoimmunity [92].
Therefore, iron deficiency is associated with several autoimmune diseases, but iron deficiency may be the effect rather than the cause. However, not all autoimmune patients are anemic.
11) Linked to Rheumatoid Arthritis
Iron deficiency is found in 30 – 60% of patients with rheumatoid arthritis [93, 94], while anemia occurs in 16 – 65% of patients with rheumatoid arthritis [95, 96].
The severity of the anemia is associated with the activity of the disease [94].
In patients with rheumatoid arthritis, iron accumulates in the joints. This iron in the joint may inflame the joints by producing dangerous oxygen molecules and attracting inflammatory cells [97].
Iron supplementation could potentially decrease disease activity and joint tenderness [98, 99].
However, iron therapy in rheumatoid arthritis patients without iron deficiency may worsen joint inflammation, pain, and dysfunction [100].
12) Associated with Systemic Lupus Erythematosus
Iron deficiency is common in patients with systemic lupus erythematosus (SLE) due to heavy menstrual bleeding and increased gut blood loss, caused by the use of drugs such as aspirin and oral anticoagulants [101, 102].
Long-term anemia of chronic inflammation can also lead to iron deficiency, since, hepcidin decreases iron absorption from the gut [103, 104].
Anemia of chronic disease frequently accompanies SLE flareups and is a useful parameter of disease activity [105].
13) Linked to Inflammatory Bowel Disease
Anemia is one of the most common manifestations of inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis [106, 107].
Both iron deficiency and anemia of chronic disease contribute to the development of anemia in IBD [108, 109].
Iron deficiency occurs in about 60 – 80% of patients with IBD, and anemia occurs in approximately 30% of patients [110].
Iron deficiency anemia is due to chronic blood loss, poor dietary intake of iron, and reduced iron absorption due to tissue inflammation [106].
14) Linked to Celiac Disease
Iron deficiency is often found in patients with celiac disease [111, 112].
Iron deficiency anemia (IDA) may be the presenting clinical feature of celiac disease and may be the only symptom in some celiac patients [113, 114, 115].
IDA was reported in up to 46% of patients with celiac disease, occurring more often in adults than children [116].
IDA is most often due to increased iron loss due to intestinal bleeding, or decreased iron absorption in the gut [117, 111].
15) Linked to Autoimmune Gastritis
Autoimmune gastritis (inflammation of the stomach) is classically associated with pernicious anemia (anemia from low vitamin B12) in adults, but recent studies have reported its association with iron-deficiency anemia in both adults and children [118].
Autoimmune gastritis was present in 27% – 52% of patients with iron-deficiency anemia [119].
Decreased or absent gastric acid production due to gastritis decrease absorption of iron taken by mouth, and thus lead to iron-deficiency anemia [118, 120].
Infections that Lower Iron Levels
16) Helicobacter pylori Infection
H.pylori infection is associated with iron-deficiency anemia, particularly in children. The presence of iron deficiency is 40 % more prevalent in children infected with H.pylori than in healthy children [121].
GI bleeding and bacterial competition for iron may explain the deficiency of iron in afflicted patients [122].
17) Parasitic Infection
Subjects with intestinal parasitic infections commonly experience iron deficiency from chronic blood loss [123].
Iron Deficiency and Metabolic and Cardiovascular Health
18) Obesity
An inverse correlation between body mass and iron status has been reported in multiple observational studies in children and adults [124, 125].
Increased hepcidin production in obese people may account for this reduction of iron levels [126].
19) Impairs Thyroid Function
Deficiency of iron may have an adverse effect on thyroid function [127].
Iron deficiency decreases thyroid peroxidase function, an enzyme important in the synthesis of thyroid hormones, thereby leading to hypothyroidism (underactive thyroid) [128].
Blood T3 and T4 levels were decreased and TSH levels increased in human subjects with iron deficiency [129, 127].
Providing iron along with iodine results in greater improvements in thyroid function compared to providing iodine alone [130, 128].
20) Decreases Body Temperature
Iron-deficient patients may have a decreased ability to maintain body temperature in response to cold [131].
In both experimental animals and humans, those with iron deficiency had reduced body temperature despite increased oxygen consumption and sympathetic activity [132, 133].
21) Heart Failure
Iron deficiency is associated with cardiovascular diseases [134, 135], and is found in up to 20% of patients with heart failure [136, 137].
Among heart failure patients, iron deficiency is associated with reduced exercise capacity, impaired quality of life, increased hospitalization and risk of deaths [138, 136].
Chronic iron deficiency increases the size and weight of the heart [139, 140].
Intravenous iron supplementation improves patients symptoms, functioning, quality of life, and reduces the need for hospital admissions among heart failure patients [141, 142].
The European Society of Cardiology Guidelines for heart failure recommend an evaluation of iron status in all patients with suspected heart failure [143].
On the other hand, increased iron stores may be associated with an increased risk of heart diseases, especially in men and menopausal women.
Iron deposition can also result in heart failure and produce irregular heart rhythms [144, 138].
22) Worsens Blood Pressure Medications (ACE inhibitor)-induced Cough
A dry cough is a common side effect of blood pressure-lowering drugs that are angiotensin-converting enzyme (ACE) inhibitors, such as Capoten and Vasotec.
An ACE inhibitor-induced cough may be associated with excessive production of dangerous nitrogen molecules in bronchial cells caused by iron deficiency.
Iron deficiency impairs the protective mechanisms of airway lining [145].
Iron supplementation successfully decreases ACE inhibitor-induced cough [146].
23) Increases Risk of Stroke
Studies in children as well as adults, particularly women, showed an association between stroke caused by blood clotting (ischemic stroke) and iron deficiency anemia [147, 148, 149].
Previously healthy children with stroke were 10 times more likely to have iron deficiency anemia than healthy children without stroke [150].
Iron deficiency is also associated with abnormal platelet levels and platelet dysfunction, which can increase the risks of stroke [151, 152, 153].
Thrombocytosis due to iron deficiency anemia is a rare but recognized cause of stroke [154].
Other Negative Effects of Iron Deficiency
24) Pica
Iron deficiency anemia is significantly associated with pica, a condition where patients develop unusual cravings for nonfood items like ice and dirt [155].
25) May Cause Restless Leg Syndrome
Restless legs syndrome (RLS), also called Willis-Ekbom disease, is characterized by an urge to move the legs and transient relief with movement.
The symptoms occur at rest, are worst at night, and often interfere with sleep [156].
RLS occurs four to five times more frequently in patients with decreased blood and brain iron levels [157, 158, 159, 160].
Studies have shown that decreased blood ferritin levels were associated with increased severity of RLS symptoms [161, 162, 163].
Iron deficiency may be involved in disease development, possibly by affecting the production of the neurotransmitter dopamine [164].
The treatment of RLS includes iron therapy and the use of drugs like dopamine agonists [156].
Iron supplementation improves RLS symptoms.
It might also improve sleep, depression, fatigue, and quality of life in RLS patients [165, 158, 166].
26) Decreases Physical Performance
Iron deficiency can affect physical performance by:
- lowering tissue cytochrome c and muscle myoglobin to about 50% of the normal values [167, 168, 169]
- decreasing oxygen uptake and use by muscles [170, 171, 172, 173]
- reducing oxygen supply to the heart and muscles, resulting in fatigue and decreased exercise performance [170, 174]
Work performance in anemic individuals may be improved with iron supplementation.
The increase in physical performance was about 4% higher in men and about 12% higher in women in individuals supplemented with iron [175, 176].
Iron deficiency anemia is found in 2% of male and in 2.5% of female athletes because heavy athletic training increases iron need.
Athletes also have a significant decrease in red blood cell number, hemoglobin and ferritin levels [177].
27) Iron is Lower in Fibromyalgia
Low blood ferritin is associated with a 6.5 fold increased risks for fibromyalgia. This could be because iron is required for the production of serotonin, dopamine, and norepinephrine, which were found to be low in the cerebrospinal fluid of fibromyalgia patients [178].
28) Causes Fatigue
Iron deficiency could have an effect on fatigue in nonanemic women of childbearing age [179, 180].
Its deficiency increased fatigue and decreases the quality of life in women [181].
Iron supplementation for 12 weeks decreased fatigue by almost 50% in menstruating iron-deficient nonanemic women [182, 183].
29) Lung Diseases
Iron deficiency is more common in patients with chronic obstructive pulmonary disease (COPD) than in those without the lung condition [184].
Iron deficiency is associated with [184, 185, 186, 187]:
- decreased blood oxygen levels
- worsening of COPD symptoms
- decreased exercise intolerance
- poor clinical outcome for COPD
- high blood pressure in the lungs without known causes (idiopathic pulmonary arterial hypertension)
Treating iron deficiency and anemia in COPD patients may reduce shortness of breath [188].
It is associated with lower exercise capacity, disease severity and poor clinical outcome.
Treatment of iron deficiency may improve high blood pressure in the lungs [189].
32% of pediatric and 60% of adult cystic fibrosis patients are deficient in iron, and the iron deficiency is associated with the severity of the disease [190].
30) May Play a Role in Hair Loss
Iron may play a role in hair loss in premenopausal women [191].
Studies reported that 72% of women with hair loss had lower blood ferritin levels [192, 193].
Iron supplementation can help reduce hair loss [194].
In a study, 18 women with hair loss experienced 100% hair regrowth in after taking oral iron therapy. The hair loss recurred when iron therapy was discontinued [195].
Hair follicle cells are sensitive to decreased iron, thus resulting in decreased hair growth in the presence of iron deficiency [195].
However, other studies showed no association between iron deficiency and female hair loss [196]. Therefore, currently, there is not sufficient evidence to recommend screening for iron deficiency in patients with hair loss or to recommend giving iron supplementation to patients with hair loss and iron deficiency [197].
31) Decreases Appetite
Iron deficiency is associated with decreased appetite and growth in children [198].
Iron deficiency increases leptin, which reduces appetite and food intake [199].
Iron controls leptin levels. Blood ferritin decreases with increased blood leptin levels [200, 199].
32) Iron is Very Low in Chronic Kidney Disease (CKD)
33) May Worsen Toxic Effects of Lead Poisoning
Iron deficiency and lead poisoning are common among children in many parts of the world, especially children between the ages of 1 and 2 years [202, 203, 204].
Children with iron deficiency are more likely to have elevated blood lead levels [205, 206, 207].
Iron deficiency increases lead absorption, thus enhancing the toxic effects of lead [208, 209, 210].
Lead poisoning and iron deficiency adversely affect red blood cell production (erythropoiesis) [211, 212].
Both iron deficiency anemia and lead poisoning lead to impaired brain development, lower intelligence, and reduced muscle function and physical activity [213, 214, 215].
An adequate intake of dietary iron is strongly recommended in order to lower blood lead levels and prevent the toxic effects of lead exposure [216, 217].
However, some studies suggest that therapeutic iron may actually interfere with lead excretion and elevate lead levels [218, 219].
4-Part Series
This post is part of a 4-part series about iron.
Part 1: Iron Metabolism, Lab Tests, Iron Deficiency Anemia and Overload
Part 2: 47 Negative Health Effects of Iron Deficiency
Part 3: Iron Sources, and Ways to Increase or Decrease Iron
Part 4: Negative Health Effects of High Iron
Low Iron Levels?
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