Iron Supplements: Benefits, side-effects, dosage and research

Iron, which has a chemical symbol of Fe, is a critical mineral that ensures the blood cells in the body are healthy. 

When the body lacks iron, this results in iron deficiency anaemia, which affects approximately 17% of the world’s population [1]. About 3.4% of the US population has iron-deficiency anaemia, while 16.7% of the people in Europe have the same condition [1]. In Asia, 47.7% of the population has iron-deficiency anaemia, which is considered a treatable condition. 

Iron-deficiency anaemia is recognized as the most common nutritional deficiency globally. It causes lightheadedness and extreme fatigue. Although it affects people of all ages, it is more common in the following groups: 

  • Children 
  • Pregnant women 
  • Menstruating women 
  • Elderly 
  • People receiving kidney dialysis 
  • Vegetarians 
  • Endurance athletes 

Children – Children and infants have higher requirements for iron due to their rapid growth. 

Pregnant womenWomen who are pregnant have an increased need for iron to keep up with the demands of the growing foetus. Production of red blood cells in the growing foetus can deplete the mother’s iron stores. Hence, there is a need for supplemental iron or increased iron intake from food. Doctors routinely indicate prenatal vitamins and iron to prevent infants’ low birth weight or premature birth. 

It is recommended that when women get pregnant, they should take at least 30 mg of supplemental iron daily [2]. 

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Menstruating women – Women who menstruate and soak pads once every hour or who menstruate for at least seven days are at increased risk of iron deficiency anaemia. 

Vegetarians Vegetarians are at increased risk of iron deficiency anaemia if they do not have sufficient non-heme iron intake from the plants or vegetables they eat. It should be noted that non-heme iron is not efficiently absorbed in the body. Hence, vegetarians would need to eat a considerable amount of plant-based sources that are rich in iron. They can also take vitamin C to increase the uptake of non-heme iron. 

Supplementation with iron could reduce the risk of iron deficiency anaemia among vegetarians. 

Elderly – Older adults are at risk of anaemia due to chronic inflammatory diseases and risks of poor nutrition. 

People on dialysisOne of the hormones present in the kidney is called erythropoietin, which is responsible for making red blood cells. Failure of the kidney reduces the ability of the kidneys to produce erythropoietin and red blood cells. In turn, this leads to anaemia. Further, during hemodialysis, patients can experience some blood loss. 

Endurance athletes can suffer from faster hemolysis or breakdown of red blood cells compared to non-athletes. Menstruating female athletes are also at increased risk of iron deficiency anaemia. 

Iron is a central component of protein present in red blood cells called haemoglobin. This protein has an important role in carrying oxygen from the lungs to all cells in the body. An iron deficiency can affect the population of red blood cells as there will not be enough red blood cells to carry oxygen. In turn, this lack of iron leads to fatigue. 

Apart from being a main component of haemoglobin, it is also a significant component of myoglobin, a protein in muscle tissues that carry and store oxygen. 

Iron is crucial for the healthy development of the brain and growth in children. It also has a role in the production and function of various hormones and cells. 

Iron from food is present in two forms: 

  • Non-heme 
  • Heme 

What are the sources of heme iron? 

Heme is present only in the following foods: 

  • Beef or chicken liver 
  • Organ meats 
  • Oysters, mussels, clams 
  • Beef
  • Canned light tuna 
  • Canned sardines 
  • Poultry 

What are the sources of non-heme iron? 

Here are some foods rich in non-heme iron 

  • Grains
  • Nuts
  • Legumes 
  • Seeds
  • Leafy greens 
  • Fortified foods 

When present in the body, iron is stored as ferritin. Ferritin is found in the following organs of the body: 

  • Liver
  • Muscle tissue 
  • Spleen 
  • Bone marrow 

Ferritin is transported throughout the body through a protein called transferrin. When anaemia is suspected, doctors check for the levels of ferritin and transferrin in the body. 

What are the benefits of iron supplementation?

Iron supplementation is necessary to restore low levels of iron in the body. Alleviation of iron deficiency can also reduce symptoms associated with iron deficiency anaemia. It can also prevent complications due to a prolonged lack of iron. 

Here are some benefits of iron supplementation: 

Anaemia 

Supplementation with iron is necessary for iron deficiency anaemia. Although there are multiple reasons for anaemia, low iron levels are the most common cause. 

Iron deficiency can lead to the following if left untreated: 

  • Heart murmur 
  • Enlarged heart 
  • Arrhythmias 
  • Heart failure 
  • Increased risk of fibromyalgia 
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A study [3] suggests that iron is a cofactor for enzymes responsible for synthesizing serotonin, dopamine metabolites, and norepinephrine. Further, a lack of iron also leads to the underutilization of tryptophan, a serotonin precursor. When serotonin levels are low, this can lead to several clinical manifestations of fibromyalgia. 

Fibromyalgia symptoms include pain and stiffness all over the body, depression and anxiety, fatigue and tiredness, sleep problems, headaches, migraine, and problems with memory, concentration, and thinking. 

Further, iron deficiency in patients with fibromyalgia may decrease the transport of oxygen and the function of mitochondria in the muscles. In turn, this could affect patients’ physical functioning and exercise performance and cause frequent fatigue, which is the most common symptom of fibromyalgia. Iron supplementation is suggested to reduce the risk of fibromyalgia. 

Apart from fibromyalgia, daily supplementation with iron can also treat low iron status in menstruating individuals. 

Fatigue 

Individuals who are not diagnosed with anaemia but have low ferritin levels could exhibit fatigue. Iron can help manage fatigue. 

Improvement in athletic performance 

Athletes require sufficient oxygen in their muscles to produce energy and increase their stamina and power. Myoglobin in the muscles is responsible for supplying oxygen to the muscles. An increased need for oxygen means that athletes would also require higher levels of iron to produce myoglobin. A sufficient amount of iron would ensure that athletes have a ready supply of myoglobin to keep up with oxygen and energy demands. 

Better cognition 

Evidence [4] from studies has shown that micronutrient deficiencies, especially related to reduced iron levels in the body, are linked to cognitive impairments. These deficiencies are also associated with potential long-term behavioural changes. Cognitive impairments related to poor attention span, impairment in sensory perception functions and intelligence are some of the conditions seen in those with iron deficiency anaemia. 

In addition, iron deficiency, even without anaemia, can also cause cognitive disturbances. This suggests that once iron levels drop in the blood, this can immediately affect attentiveness and concentration. Restoring iron to normal levels can boost mental performance and improve cognition [4]. 

A study [5] of adolescent girls who had low levels of iron but no iron deficiency anaemia found that girls who received 650 mg of oral ferrous sulphate twice a day for eight weeks significantly performed better in tests on memory and verbal learning compared to the control group. 

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This study, published in The Lancet, randomized 81 adolescent girls from a Baltimore school who had low levels of ferritin and haemoglobin at baseline into an experimental and control group. 

There were no significant differences in the cognitive test scores, haemoglobin concentrations, serum ferritin concentrations, mean age, and ethnic distribution of the participants at baseline. Participants in the control and experimental groups had similar characteristics, which is essential in removing any factors that might confound or introduce bias in the study results. 

The study showed that supplementation with iron could improve memory and verbal learning after just eight weeks of supplementation in an urban population of high school girls who had non-anaemic iron deficiency. 

It is observed that young women and adolescent girls are at higher risk of getting iron deficiency anaemia due to menstrual losses, increased iron demands to meet puberty needs, and limited dietary iron intake. Iron deficiency can range among adolescent girls from 9% to 40%, depending on the criteria used and the population studied. 

Are there any side effects?

The tolerable upper intake level (UL) of elemental iron is 45 mg daily. Iron is safe for most people who take iron supplements not exceeding 45 mg daily. 

When taken in amounts higher than UL, it can cause side effects such as vomiting and stomach upset. Taking these supplements along with food decreases side effects. However, food can also reduce the ability of the body to absorb iron well. Doctors or healthcare practitioners should constantly monitor patients who are above the recommended dose or above the UL. When taken in excessive amounts, elemental iron is likely, not safe. 

An elemental iron of less than 45 mg daily is safe in pregnant women. However, excessive amounts might increase the risk of preterm birth. 

Children taking iron supplements below 40 mg daily, which is the UL for iron in children, would be safe. But higher doses of iron may cause poisoning death. It has been shown that 60 mg/kg doses could be fatal. For instance, a 30 kg child taking 1800 mg of iron daily could die of iron poisoning. 

Premature infants with low vitamin E levels can suffer from serious problems when given iron supplementation. These infants are at increased risk of hemolytic anaemia when given excess iron. Iron supplementation should be delayed until four to six weeks since serum iron in infants is elevated in the first four weeks, even without supplementation. 

Treating vitamin E deficiency is necessary before iron supplementation. However, too much vitamin E can decrease the absorption of iron. Restoring vitamin E to appropriate levels in premature infants would help increase iron absorption and reduce the risk of hemolytic anaemia. 

Another common side effect of iron supplementation is constipation. When experiencing constipation, include fibre in your diet and enough water to loosen stools. However, if constipation remains a problem after adjusting your diet, talk to your doctor if it is appropriate to take a stool softener. 

When iron is sourced from the diet, the risk of iron overload is low in most adults. Instead, the body stores excess iron for future use. 

People with genetic disorders that increase iron absorption can experience iron overload. One of these genetic disorders includes hemochromatosis, where iron is stored excessively in the body. In this case, iron supplementation is not recommended. 

In rare cases, iron supplementation results in coma, seizure, internal bleeding, and even death. 

What is the recommended dosage?

Recommended dietary allowance (RDA) differs between gender and age. 

  • Infants who are 7-12 months old should take 11 mg of iron daily
  • Children who are aged 1-13 years old are advised to take 7 mg of iron daily 
  • Males 14-18 years old should take 11 mg daily
  • Males 19 and older should take 8 milligrams daily 
  • Females aged 14-18 years old should take 15 milligrams daily 
  • Females 19 to 50 years old should take 18 milligrams daily 
  • Females in menopause should take 8 milligrams daily 

The requirement for iron increases to 27 mg daily for pregnant women and 9 to 10 mg daily for people who breastfeed. 

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The tolerable upper limit for iron in adolescents and adults is 45 mg daily and 40 mg daily for children.

To treat iron deficiency, doctors recommend 50 to 100 mg daily divided into two to three doses. When diagnosed with iron deficiency, always consult your doctor and follow the provider’s advice and guidance when taking iron supplements. 

Taking iron supplements with food is recommended. To increase absorption, healthcare providers recommend taking these supplements with vitamin C. However, a recent randomized controlled trial [6] published in the Journal of the American Medical Association Network showed no difference in the absorption of iron in those who took this supplement alone and patients who took an iron supplement with vitamin C. These findings suggest that vitamin C supplements are not essential for iron deficiency and iron deficiency anaemia when taking oral iron supplements. 

Interactions with other drugs and food 

Absorption of iron supplements is reduced when consuming the following foods: 

  • Cereal 
  • Eggs
  • Coffee
  • Green teas or black teas 
  • Soy protein 

When taking calcium supplements for other conditions, it is necessary to take iron and calcium supplements at different times of the day. Calcium has been shown to interfere with the absorption of iron. 

Meanwhile, iron supplements are also found to interfere with the absorption of certain micronutrients. Specific micronutrients that might not be adequately absorbed when taking iron include the following: 

  • Manganese 
  • Copper 
  • Zinc
  • Magnesium 

Meanwhile, individuals taking antacids for prolonged periods are at increased risk of iron deficiency. Antacids can reduce stomach acidity required for iron absorption in the body. 

Iron supplements also interact with the following medications: 

  • Iron might decrease antibiotic absorption, which can affect these antibiotics’ effectiveness. Antibiotics that can interact with iron include quinolone and tetracycline antibiotics. To avoid iron and antibiotic interaction, it is recommended that iron supplementation should be taken two hours before or two hours following the intake of antibiotics. 
  • Penicillamine, sold under Cuprimine, is used to treat Wilson’s disease. This disease is a rare genetic disorder where the body stores excess tissues. Tissues where copper is stored in excess, include the corneas of the eyes, liver, and brain tissues. Left untreated can cause central nervous system dysfunction, liver dysfunction, and even death. When taken with iron, penicillamine attaches to iron, reducing the absorption of both substances. Hence, taking iron two hours before or after the intake of penicillamine is recommended. 
  • Levothyroxine is a medication used to treat thyroid hormone deficiency. However, iron bonds with levothyroxine, impairing or limiting its absorption in the body. Hence, it is recommended that iron be taken at least four hours before or after levothyroxine intake. 
  • Carbidopa and levodopa are drugs used in combination to treat Parkinson’s disease. Symptoms of Parkinson’s disease have been shown to worsen when taking iron supplementation; levels of carbidopa and levodopa are reduced by 50% to 70%, respectively, when taking iron supplements. It is recommended that iron should be taken several hours before and after taking both levodopa and carbidopa. 
  • Carbamazepine is used to treat bipolar disorder and certain types of seizures. It has been shown that iron reduces the oral bioavailability of carbamazepine. Hence, taking iron supplements several hours before and after the intake of carbamazepine would be necessary. 
  • Angiotensin-converting enzymes (ACE) inhibitors are used to treat hypertension. Taking iron supplements two hours before and after intake of ACE inhibitors would lessen or prevent ACE-iron interaction. 

Iron supplements 

Iron supplements contain iron combined with another compound. Here are some examples of common iron supplement compounds: 

  • Ferrous sulfate 
  • Ferrous succinate 
  • Ferrous gluconate 
  • Ferrous fumarate 

The amount of iron in a supplement differs from the compound. For example, ferrous sulfate is only composed of 20% iron, while ferrous succinate has 35% elemental iron. Ferrous fumarate is 33% elemental iron, while ferrous gluconate has only 12% elemental iron. 

Always check the supplement facts to determine the amount of iron in milligrams in your supplements. 

A medical professional will help you choose the best iron supplement and monitor its effects on your body. 

Research on iron

A clinical trial [6] study protocol is recently published. It aims to examine if every other-day supplementation with iron is more effective or equally effective than daily iron supplementation in treating iron deficiency anaemia. For iron deficiency anaemia patients, the first line of treatment remains oral supplementation with elemental iron. However, more studies still need to be conducted to determine the appropriate oral iron dosage and regimen. The proposed clinical trial aims to answer these questions and determine the feasibility, side effects and safety profile of every other day oral iron supplementation. 

New knowledge on iron supplementation includes information that vitamin C may no longer be needed to increase oral iron absorption. However, earlier evidence [7] has shown that vitamin C or taking orange juice with oral iron supplements could increase iron absorption. There is still a need to conduct more trials to determine if vitamin C is no longer needed to increase iron absorption in the body. 

Apart from oral supplementation, intravenous iron supplementation is now used for certain groups of patients [7]. Intravenous iron administration is recommended for the following groups of patients or individuals: 

  • Individuals who cannot tolerate oral supplementation of iron due to its side effects 
  • Pregnant women who have severe morning sickness
  • Patients who have had gastric bypass surgery. These individuals have reduced gastric secretion, which impairs the absorption of elemental iron. 
  • People who have malabsorption conditions that prevent the adequate absorption of elemental iron. These include those who have celiac disease, Whipple’s disease, and pernicious anaemia. 
  • Individuals suffering from chronic inflammation states such as rheumatoid arthritis and systemic lupus erythematosus. Those who have these conditions have elevated hepcidin levels, which in turn reduce the absorption of oral iron. 

Anaemia remains to be a global health issue. Healthcare providers must monitor and determine if a patient responds well to oral supplementation. However, if an individual is not responding well to oral supplements, other routes of administration should be considered. 

Take home message 

Iron remains a vital mineral the body needs to optimize health and well-being. Iron is required to ferry oxygen from the blood to different cells in the body. It is also necessary to form myoglobin, the protein-iron complex in the muscles responsible for storing and diffusing oxygen to the muscle cells. 

When left untreated, iron deficiency can develop into iron-deficiency anaemia. Currently, there are different iron supplements used to treat iron deficiency anaemia. Iron is a compound and includes ferrous sulfate, ferrous gluconate, ferrous fumarate, and ferrous succinate. The amount of iron differs between these compounds. Hence, it is crucial to examine the amount of iron in your supplements. Always consult your doctor to determine the appropriate amount of iron supplements you are taking. Since there are differences in the amount of iron in available iron supplements, talk to your doctor about which iron supplement is best for you. 

If you are not anaemic or iron deficient, there is no need to take iron supplements. However, if you have iron deficiency or iron deficiency anaemia, avoid taking more than 45 milligrams of iron daily. The TUL for iron in adults is 45 milligrams daily. 

An ideal iron supplement should be readily absorbed, high quality, and a good value for the cost. It should also have minimal side effects only. One of the most common side effect of supplementation with iron is constipation. When constipated, increase the amount of fibre in your diet and drink plenty of water to soften your stool. However, if you have prolonged constipation, talk to your doctor immediately and determine if you can take stool softeners. 

Iron deficiency can affect your physical health, with fatigue and impaired cognitive abilities as the most common symptoms of iron deficiency. When left untreated, iron deficiency anaemia can have serious side effects, which include arrhythmia of the heart. Hence, monitoring your iron levels through a thorough laboratory check-up is essential. If you are pregnant, breastfeeding or menstruating heavily, you are at increased risk of iron deficiency and iron deficiency anaemia. Hence, talking to your doctor once you experience any of the signs and symptoms of iron deficiency would help prevent any adverse effects of anaemia. 

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[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3685880/ 
[2] https://ods.od.nih.gov/factsheets/Iron-HealthProfessional/ 
[3] https://www.nature.com/articles/s41598-021-89842-9#Sec2 
[4] https://www.dovepress.com/iron-deficiency-and-cognitive-functions-peer-reviewed-fulltext-article-NDT 
[5] https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(96)02341-0/fulltext 
[6] https://pilotfeasibilitystudies.biomedcentral.com/articles/10.1186/s40814-022-01042-y 
[7] https://www.ncbi.nlm.nih.gov/books/NBK557376/ 

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