Iron is one of the most abundant minerals on Earth. It occurs naturally in various foods such as oysters, legumes, <a href="/foods/chocolate/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Chocolate&lt;/h6&gt;&lt;p&gt;Chocolate is made from roasted and ground cacao seeds (aka beans) and has been consumed by cultures around the world for centuries. Cacao is thought to have health benefits due to its high content of polyphenols and flavonoids.&lt;/p&gt;&lt;/div&gt;">chocolate</a>, spinach, beef, and <a href="/foods/potatoes/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Potatoes&lt;/h6&gt;&lt;p&gt;Potatoes are starchy tubers that contain a modest amount of complete protein and a broad array of vitamins and minerals. When eaten boiled or baked without calorie-dense toppings, they are among the most filling foods per calorie, but when fried they are less filling and are associated with an elevated risk of weight gain, type 2 diabetes, and cardiovascular disease in observational studies.&lt;/p&gt;&lt;/div&gt;">potatoes</a>, and is added to some foods (e.g., cereals) as a fortification measure. Iron is also sold as a supplement in the form of capsules, tablets, or liquid. In hospital settings, it can be administered through intravenous (IV) or intramuscular (IM) injection.<a href="#ref-1" id="ref-link-1" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;&lt;a href="https://ods.od.nih.gov/factsheets/iron-HealthProfessional/" target="\_blank" rel="noopener noreferrer"&gt;Iron Fact Sheet for Health Professionals. MedlinePlus. National Institutes of Health (NIH) Office of Dietary Supplements (ODS). Updated 2023 Jun 15; cited 2023 December 5
&lt;/a&gt;&lt;/p&gt;&lt;/div&gt;'>[1]</a>
Dietary iron comes in two primary forms: heme iron and non-heme iron. Heme iron is more readily absorbed; it is formed when iron binds to a heterocyclic organic compound called porphyrin. Heme iron is a component of hemoproteins like <a href="/outcomes/hemoglobin/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Hemoglobin&lt;/h6&gt;&lt;p&gt;Hemoglobin is the protein that carries oxygen in red blood cells for delivery to tissues throughout the body.&lt;/p&gt;&lt;/div&gt;">hemoglobin</a> (Hb), an oxygen transport protein, and <a href="/outcomes/myoglibin/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Myoglobin&lt;/h6&gt;&lt;p&gt;Myoglobin is like the &quot;muscle version&quot; of hemoglobin: it is an iron- and oxygen-binding protein found in muscles, whose function is to store oxygen (in contrast to hemoglobin, whose function is to transport it). Myoglobin's oxygen affinity is higher than hemoglobin's.&lt;/p&gt;&lt;/div&gt;">myoglobin</a>, an oxygen-storage protein found in muscle tissues. Animal products (e.g., meat, poultry, and fish) contain both heme and non-heme iron, whereas plant-based and iron-fortified foods only provide non-heme iron, which is less easily absorbed by the body.<a href="#ref-1" id="ref-link-1" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;&lt;a href="https://ods.od.nih.gov/factsheets/iron-HealthProfessional/" target="\_blank" rel="noopener noreferrer"&gt;Iron Fact Sheet for Health Professionals. MedlinePlus. National Institutes of Health (NIH) Office of Dietary Supplements (ODS). Updated 2023 Jun 15; cited 2023 December 5
&lt;/a&gt;&lt;/p&gt;&lt;/div&gt;'>[1]</a>
Additionally, iron is a constituent of the iron-sulfur clusters (ISCs)<a href="#ref-5" id="ref-link-5" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Bandyopadhyay S, Chandramouli K, Johnson MK. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/19021507" target="\_blank" rel="noopener noreferrer"&gt;Iron-sulfur cluster biosynthesis.
&lt;/a&gt;&lt;/p&gt;Biochem Soc Trans (2008-Dec)&lt;/div&gt;'>[5]</a> found in many proteins; iron is also present in proteins responsible for iron storage and transport (i.e., <a href="/outcomes/transferrin/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Transferrin&lt;/h6&gt;&lt;p&gt;Transferrin is a protein found in the blood that plays a role in iron metabolism. Along with other biomarkers, transferrin levels can be used to assess the level of iron in the body.&lt;/p&gt;&lt;/div&gt;">transferrin</a>, <a href="/supplements/lactoferrin/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Lactoferrin&lt;/h6&gt;&lt;p&gt;Lactoferrin is an iron-binding glycoprotein found in the milk of mammals. Colostrum (the first milk after a baby is born) contains especially high levels of lactoferrin. Research suggests that lactoferrin exhibits antimicrobial, antiviral, antifungal, and antiparasitic properties.&lt;/p&gt;&lt;/div&gt;">lactoferrin</a>, <a href="/outcomes/ferritin/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Ferritin&lt;/h6&gt;&lt;p&gt;Ferritin is the primary protein for storing iron in the body. Ferritin levels are generally used as an indirect measure of iron levels (e.g., for diagnosis of anemia). However, in some conditions, ferritin levels can remain high when iron levels are low.&lt;/p&gt;&lt;/div&gt;">ferritin</a>, hemosiderin).<a href="#ref-6" id="ref-link-6" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Institute of Medicine (US) Panel on Micronutrients. &lt;a href="https://www.ncbi.nlm.nih.gov/books/NBK222309/" target="\_blank" rel="noopener noreferrer"&gt;Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Chapter 9, Iron
&lt;/a&gt;&lt;/p&gt;(2001)&lt;/div&gt;'>[6]</a>

What is iron?

Although iron is typically prescribed during pregnancy to prevent IDA,<a href="#ref-8" id="ref-link-8" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Ali SA, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/37069552" target="\_blank" rel="noopener noreferrer"&gt;Role of iron in the reduction of anemia among women of reproductive age in low-middle income countries: insights from systematic review and meta-analysis.
&lt;/a&gt;&lt;/p&gt;BMC Womens Health (2023-Apr-17)&lt;/div&gt;'>[8]</a><a href="#ref-9" id="ref-link-9" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Hansen R, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/37403900" target="\_blank" rel="noopener noreferrer"&gt;Iron supplements in pregnant women with normal iron status: A systematic review and meta-analysis.
&lt;/a&gt;&lt;/p&gt;Acta Obstet Gynecol Scand (2023-Sep)&lt;/div&gt;'>[9]</a> regardless of the mother’s iron levels, more studies should be conducted to verify its benefits throughout pregnancy and after childbirth.
One meta-analysis has assessed the effect of daily iron supplementation in pregnant iron-replete women and found that it may reduce both maternal IDA and maternal ID at term (i.e., at 37 weeks gestation or later). The results also suggested that daily oral iron supplementation may decrease the risk of newborns being small for gestational age (SGA) (i.e., having a birth weight below the 10th percentile for their gestational age) or low birthweight (LBW) (i.e., having a birth weight lower than 2500 g).<a href="#ref-9" id="ref-link-9" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Hansen R, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/37403900" target="\_blank" rel="noopener noreferrer"&gt;Iron supplements in pregnant women with normal iron status: A systematic review and meta-analysis.
&lt;/a&gt;&lt;/p&gt;Acta Obstet Gynecol Scand (2023-Sep)&lt;/div&gt;'>[9]</a> Another meta-analysis, which included pregnant and non-pregnant women of reproductive age with IDA, found a significant increase in hemoglobin and ferritin levels following iron supplementation.<a href="#ref-8" id="ref-link-8" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Ali SA, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/37069552" target="\_blank" rel="noopener noreferrer"&gt;Role of iron in the reduction of anemia among women of reproductive age in low-middle income countries: insights from systematic review and meta-analysis.
&lt;/a&gt;&lt;/p&gt;BMC Womens Health (2023-Apr-17)&lt;/div&gt;'>[8]</a> However, both meta-analyses presented high heterogeneity, risk of bias, and low to moderate levels of evidence, leaving some questions about the benefits and safety of preventative iron supplementation unanswered.

Does iron supplementation improve pregnancy outcomes?

Oral iron replacement therapy is typically the first-line treatment for IDA. Iron is available in different forms (e.g., tablets, liquid) and compounds (e.g., ferrous sulfate, ferrous fumarate, ferrous bisglycinate, etc.), each of which provides different amounts of elemental iron.<a href="#ref-23" id="ref-link-23" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Arulparithi CS, Arunbabu T, Manjani S. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/37209050" target="\_blank" rel="noopener noreferrer"&gt;Iron Preparations in the Management of Iron Deficiency Anemia in Infants and Children: A Systematic Review and Meta-Analysis.
&lt;/a&gt;&lt;/p&gt;Indian Pediatr (2023-Sep-15)&lt;/div&gt;'>[23]</a>
Here are some of the most common forms of iron found in supplements:
<table class="table table-bordered markdown-table">
<thead>
<tr>
<th>Iron salt form</th>
<th>Elemental iron (%)</th>
<th>Elemental iron (mg)</th>
</tr>
</thead>
<tbody>
<tr>
<td>Ferrous sulfate</td>
<td>20</td>
<td>64</td>
</tr>
<tr>
<td>Ferrous fumarate</td>
<td>33</td>
<td>99</td>
</tr>
<tr>
<td>Ferrous gluconate</td>
<td>12</td>
<td>39</td>
</tr>
</tbody>
</table>
Formulations containing ferrous iron (Fe2+) are more bioavailable, but they are also more likely to cause side effects. In contrast, ferric iron (Fe3+) preparations are usually better-tolerated but not as effective.<a href="#ref-4" id="ref-link-4" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Aksu T, Ünal Ş. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/37357449" target="\_blank" rel="noopener noreferrer"&gt;Iron Deficiency Anemia in Infancy, Childhood, and Adolescence.
&lt;/a&gt;&lt;/p&gt;Turk Arch Pediatr (2023-Jul)&lt;/div&gt;'>[4]</a>
Ferrous bisglycinate is another popular iron form found in supplements, wherein iron is chelated to two glycine molecules. Ferrous bisglycinate is marketed as more bioavailable than the other iron salts, and as having fewer gastrointestinal side effects. Furthermore, due to its stable chemical structure, ferrous bisglycinate is less affected by common iron absorption inhibitors (e.g., phytates found in cereals). However, although results from a meta-analysis showed that while iron bisglycinate was more effective than other iron salts in increasing hemoglobin levels in pregnant women, in children its effectiveness was comparable to other iron preparations.<a href="#ref-24" id="ref-link-24" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Fischer JAJ, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/36728680" target="\_blank" rel="noopener noreferrer"&gt;The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials.
&lt;/a&gt;&lt;/p&gt;Nutr Rev (2023-Jul-10)&lt;/div&gt;'>[24]</a>
Heme iron polypeptide (HIP) is another form of iron. It is commonly produced from swine or bovine blood using enzymatic hydrolysis, in which heme iron is bound to peptides derived from the digested hemoglobin.<a href="#ref-25" id="ref-link-25" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Tansukkasem S, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/37685181" target="\_blank" rel="noopener noreferrer"&gt;Production and Characterization of Heme Iron Polypeptide from the Blood of Skipjack Tuna () Using Enzymatic Hydrolysis for Food Supplement Application.
&lt;/a&gt;&lt;/p&gt;Foods (2023-Aug-29)&lt;/div&gt;'>[25]</a> This form of iron has increased in popularity due to claims that it has enhanced bioavailability and fewer gastrointestinal side effects than other iron compounds. One study showed that when compared to ferrous fumarate, HIP taken with meals significantly increased iron absorption, but was not associated with side effects.<a href="#ref-26" id="ref-link-26" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Seligman et al.. &lt;a href="https://doi.org/10.1016/S0271-5317(00)00215-3" target="\_blank" rel="noopener noreferrer"&gt;Clinical studies of hip: An oral heme-iron product
&lt;/a&gt;&lt;/p&gt;Nutrition Research (2000-09-01)&lt;/div&gt;'>[26]</a> However, larger studies should be conducted to compare its efficacy and safety to other iron preparations.
When iron is administered intravenously, IV ferric carboxymaltose and IV iron sucrose appear to be the most effective forms at increasing hemoglobin and ferritin levels within a period of four weeks.<a href="#ref-27" id="ref-link-27" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Rogozińska E, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/34171281" target="\_blank" rel="noopener noreferrer"&gt;Iron preparations for women of reproductive age with iron deficiency anaemia in pregnancy (FRIDA): a systematic review and network meta-analysis.
&lt;/a&gt;&lt;/p&gt;Lancet Haematol (2021-Jul)&lt;/div&gt;'>[27]</a>
Finally, one <a href="/glossary/in-vitro-study/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;In Vitro Study&lt;/h6&gt;&lt;p&gt;&lt;em&gt;In vitro&lt;/em&gt; (Latin for “within the glass”) refers to studies that are performed outside of a living organism. In scientific research, this often involves performing experiments on bacterial, animal, or human cells growing in lab culture dishes.&lt;/p&gt;&lt;/div&gt;">in vitro</a> study compared modified-release iron supplements to immediate-release formulations and found that the slow-release tablets did not completely dissolve even after 24 hours, and iron uptake was considerably lower compared to regular tablets.<a href="#ref-28" id="ref-link-28" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Zariwala MG, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/24482777" target="\_blank" rel="noopener noreferrer"&gt;Comparison study of oral iron preparations using a human intestinal model.
&lt;/a&gt;&lt;/p&gt;Sci Pharm (2013)&lt;/div&gt;'>[28]</a> Although modified-release iron preparations may be better tolerated, with fewer side effects, they may not be as effective. These findings need further clarification through in vivo clinical studies.

How do different iron forms compare?

It remains unclear whether iron supplementation is beneficial for athletes with ID but not anemia, or for those with normal iron status. While there is some evidence that iron supplementation may improve fatigue in iron-deficient athletes and non-athletes,<a href="#ref-7" id="ref-link-7" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Houston BL, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/29626044" target="\_blank" rel="noopener noreferrer"&gt;Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials
&lt;/a&gt;&lt;/p&gt;BMJ Open (2018 Apr 5)&lt;/div&gt;'>[7]</a> and intensive training is a potential cause of iron depletion,<a href="#ref-52" id="ref-link-52" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Wouthuyzen-Bakker M, van Assen S. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/25918331" target="\_blank" rel="noopener noreferrer"&gt;Exercise-induced anaemia: a forgotten cause of iron deficiency anaemia in young adults.
&lt;/a&gt;&lt;/p&gt;Br J Gen Pract (2015-May)&lt;/div&gt;'>[52]</a> only a few studies have investigated the benefits of iron supplementation in athletes with adequate iron levels to replenish iron loss due to training.
In one study involving iron-sufficient soccer players during training, iron supplementation was found to maintain ferritin and iron store levels, and these levels decreased once the supplementation was interrupted.<a href="#ref-53" id="ref-link-53" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Escanero JF, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/9284502" target="\_blank" rel="noopener noreferrer"&gt;Iron stores in professional athletes throughout the sports season.
&lt;/a&gt;&lt;/p&gt;Physiol Behav (1997-Oct)&lt;/div&gt;'>[53]</a> However, this study did not observe any significant difference in transferrin levels, which provide information on the iron levels required for erythropoiesis (red blood cell production), and it lacked a control group.
In another study, swimmers between the ages of 12 and 17 were either given an iron supplement (47 mg iron daily) or instructed to consume an iron-rich diet. Both interventions failed to significantly alter either the participants’ iron status (measured as iron, ferritin, and transferrin levels) or their athletic performance.<a href="#ref-54" id="ref-link-54" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Tsalis G, Nikolaidis MG, Mougios V. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/15162251" target="\_blank" rel="noopener noreferrer"&gt;Effects of iron intake through food or supplement on iron status and performance of healthy adolescent swimmers during a training season.
&lt;/a&gt;&lt;/p&gt;Int J Sports Med (2004-May)&lt;/div&gt;'>[54]</a>

What is the impact of iron on physical activity?

While most people obtain adequate iron from their diet, there are situations where iron supplementation may be required.<a href="#ref-1" id="ref-link-1" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;&lt;a href="https://ods.od.nih.gov/factsheets/iron-HealthProfessional/" target="\_blank" rel="noopener noreferrer"&gt;Iron Fact Sheet for Health Professionals. MedlinePlus. National Institutes of Health (NIH) Office of Dietary Supplements (ODS). Updated 2023 Jun 15; cited 2023 December 5
&lt;/a&gt;&lt;/p&gt;&lt;/div&gt;'>[1]</a> For instance, the World Health Organization (WHO) recommends daily oral iron supplementation for all children living in areas where anemia prevalence exceeds 40%.
Frequent blood donation can also deplete iron levels, potentially leading to anemia, and therefore supplementation may be necessary, especially for people at high risk of deficiency, such as women.<a href="#ref-58" id="ref-link-58" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Milman N, Kirchhoff M. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/1889481" target="\_blank" rel="noopener noreferrer"&gt;Influence of blood donation on iron stores assessed by serum ferritin and haemoglobin in a population survey of 1433 Danish males.
&lt;/a&gt;&lt;/p&gt;Eur J Haematol (1991-Aug)&lt;/div&gt;'>[58]</a><a href="#ref-59" id="ref-link-59" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Garry PJ, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/1926310" target="\_blank" rel="noopener noreferrer"&gt;A prospective study of blood donations in healthy elderly persons
&lt;/a&gt;&lt;/p&gt;Transfusion (1991 Oct)&lt;/div&gt;'>[59]</a> However, evidence that iron supplementation is effective in preserving iron levels is still weak.
Finally, individuals following a vegetarian or <a href="/diets/vegan/" class="popover" data-tooltip='&lt;div&gt;&lt;h6&gt;Vegan Diet&lt;/h6&gt;&lt;p&gt;Vegan diets exclude all animal products. Veganism has rapidly increased in popularity, although randomized trials are still few in number. Trials do show promise for a variety of outcomes, from weight loss to autoimmunity, although comparisons to other popular diets are rare. A vegan diet should be balanced and low in processed foods (e.g. a "Whole Food Plant-Based diet") for optimal results.&lt;/p&gt;&lt;/div&gt;'>vegan diet</a> may need to increase their iron intake,<a href="#ref-1" id="ref-link-1" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;&lt;a href="https://ods.od.nih.gov/factsheets/iron-HealthProfessional/" target="\_blank" rel="noopener noreferrer"&gt;Iron Fact Sheet for Health Professionals. MedlinePlus. National Institutes of Health (NIH) Office of Dietary Supplements (ODS). Updated 2023 Jun 15; cited 2023 December 5
&lt;/a&gt;&lt;/p&gt;&lt;/div&gt;'>[1]</a> mainly because plant-based foods contain non-heme iron, which is not as bioavailable as the heme iron found in meat.

Who else may benefit from iron supplementation?

Iron plays a pivotal role in numerous biological functions and is often the first-line treatment for <a href="/conditions/iron-deficiency-anemia/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Iron Deficiency Anemia&lt;/h6&gt;&lt;p&gt;Iron deficiency anemia occurs when the body does not have enough iron to produce healthy red blood cells to transport oxygen in the blood. Iron deficiency anemia can be caused by excessive blood loss or reduced iron absorption or intake. It can be treated with oral iron supplementation, though there is a wide range of individual tolerance for, and effectiveness of, iron supplements.&lt;/p&gt;&lt;/div&gt;">iron deficiency anemia</a> (IDA). While specific guidelines exist for treating IDA with iron, there is still insufficient evidence to prove the benefits of iron supplementation in individuals with iron deficiency (ID) who are not anemic.<a href="#ref-7" id="ref-link-7" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Houston BL, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/29626044" target="\_blank" rel="noopener noreferrer"&gt;Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials
&lt;/a&gt;&lt;/p&gt;BMJ Open (2018 Apr 5)&lt;/div&gt;'>[7]</a>
In clinical practice, iron is commonly prescribed to menstruating women due to the increased blood loss, and during pregnancy to meet heightened metabolic demands and prevent IDA, which could have serious consequences for both the mother and the baby.<a href="#ref-8" id="ref-link-8" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Ali SA, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/37069552" target="\_blank" rel="noopener noreferrer"&gt;Role of iron in the reduction of anemia among women of reproductive age in low-middle income countries: insights from systematic review and meta-analysis.
&lt;/a&gt;&lt;/p&gt;BMC Womens Health (2023-Apr-17)&lt;/div&gt;'>[8]</a><a href="#ref-9" id="ref-link-9" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Hansen R, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/37403900" target="\_blank" rel="noopener noreferrer"&gt;Iron supplements in pregnant women with normal iron status: A systematic review and meta-analysis.
&lt;/a&gt;&lt;/p&gt;Acta Obstet Gynecol Scand (2023-Sep)&lt;/div&gt;'>[9]</a> 
ID is also a risk factor for <a href="/conditions/heart-failure/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Heart Failure&lt;/h6&gt;&lt;p&gt;&lt;em&gt;Heart failure&lt;/em&gt; (HF), also known as &lt;em&gt;congestive heart failure&lt;/em&gt;, is a progressive condition that occurs when the heart cannot pump enough blood to oxygenate the tissues in the brain and body. It is typically caused by other heart conditions that change the heart's structure and function. Heart failure is common, and is the leading cause of hospitalization for patients over age 65 in the U.S.&lt;/p&gt;&lt;/div&gt;">heart failure</a> (HF). Iron supplementation in individuals affected by HF appears to reduce the rates of hospitalization and the severity of HF symptoms.<a href="#ref-10" id="ref-link-10" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Hamed M, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/37383191" target="\_blank" rel="noopener noreferrer"&gt;Intravenous iron therapy among patients with heart failure and iron deficiency: An updated meta-analysis of randomized controlled trials.
&lt;/a&gt;&lt;/p&gt;Heliyon (2023-Jun)&lt;/div&gt;'>[10]</a><a href="#ref-11" id="ref-link-11" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Hamza M, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/37429060" target="\_blank" rel="noopener noreferrer"&gt;Meta-Analysis of Efficacy and Safety of Intravenous Iron in Patients With Iron Deficiency and Heart Failure With Reduced Ejection Fraction.
&lt;/a&gt;&lt;/p&gt;Am J Cardiol (2023-Sep-01)&lt;/div&gt;'>[11]</a> Hemoglobin, ferritin and <a href="/outcomes/left-ventricular-ejection-fraction/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Left Ventricular Ejection Fraction&lt;/h6&gt;&lt;p&gt;Left ventricular ejection fraction (LVEF) is the capacity of the heart to 'pulse' blood out of cardiac tissue and into circulation, and is a biomarker of cardiac health. The reduction in LVEF seen during cardiac ailments tends to be a focus of rehabilitation.&lt;/p&gt;&lt;/div&gt;">left ventricular ejection fraction</a> (LVEF) levels also seem to be increased by iron,<a href="#ref-10" id="ref-link-10" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Hamed M, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/37383191" target="\_blank" rel="noopener noreferrer"&gt;Intravenous iron therapy among patients with heart failure and iron deficiency: An updated meta-analysis of randomized controlled trials.
&lt;/a&gt;&lt;/p&gt;Heliyon (2023-Jun)&lt;/div&gt;'>[10]</a> and one meta-analysis also noted that exercise capacity and quality of life were improved after iron supplementation in people with HF.<a href="#ref-11" id="ref-link-11" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Hamza M, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/37429060" target="\_blank" rel="noopener noreferrer"&gt;Meta-Analysis of Efficacy and Safety of Intravenous Iron in Patients With Iron Deficiency and Heart Failure With Reduced Ejection Fraction.
&lt;/a&gt;&lt;/p&gt;Am J Cardiol (2023-Sep-01)&lt;/div&gt;'>[11]</a>
Iron is also a key component in the brain, and studies involving children have shown that supplementation may improve memory and concentration.<a href="#ref-12" id="ref-link-12" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Gutema BT, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/37368919" target="\_blank" rel="noopener noreferrer"&gt;Effects of iron supplementation on cognitive development in school-age children: Systematic review and meta-analysis.
&lt;/a&gt;&lt;/p&gt;PLoS One (2023)&lt;/div&gt;'>[12]</a> However, more quality research is needed to verify these results.
The question of whether iron supplementation benefits infants and young adults remains a topic of debate necessitating further research. One meta-analysis, which included children and adolescents ranging from 1 month to 19 years old, found that iron supplementation increased Hb and ferritin levels, particularly with frequent supplementation over longer periods, and resulted in reduced prevalence of overall anemia, ID, and IDA.<a href="#ref-13" id="ref-link-13" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Andersen CT, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/36849195" target="\_blank" rel="noopener noreferrer"&gt;Oral iron supplementation and anaemia in children according to schedule, duration, dose and cosupplementation: a systematic review and meta-analysis of 129 randomised trials.
&lt;/a&gt;&lt;/p&gt;BMJ Glob Health (2023-Feb)&lt;/div&gt;'>[13]</a>
Finally, one meta-analysis demonstrated that both oral and IV iron supplementation appeared to improve symptoms of <a href="/conditions/restless-leg-syndrome/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Restless Leg Syndrome&lt;/h6&gt;&lt;p&gt;Restless leg syndrome (RLS) is characterized by uncomfortable sensations in the legs that are momentarily relieved upon movement. The sensations typically worsen at night when the legs are at rest, which is incredibly disruptive to sleep quality.&lt;/p&gt;&lt;/div&gt;">restless leg syndrome</a> (RLS). Specifically, IV supplementation with ferric carboxymaltose (FCM) was associated with a significant improvement in <a href="/outcomes/quality-of-life/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Quality of Life&lt;/h6&gt;&lt;p&gt;Quality of life (QOL) refers to a general, all concompassing, response as to how tolerance and enjoyable one's living conditions are. QOL is impaired in various disease states that reduce functionality or cause pain, and treating these symptoms causes an increase in QOL.&lt;/p&gt;&lt;/div&gt;">quality of life</a> (QOL) scores, although it had no noticeable effect on sleep quality.<a href="#ref-14" id="ref-link-14" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Tomer Avni, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/30798983" target="\_blank" rel="noopener noreferrer"&gt;Iron supplementation for restless legs syndrome - A systematic review and meta-analysis
&lt;/a&gt;&lt;/p&gt;Eur J Intern Med (2019 May)&lt;/div&gt;'>[14]</a>

What are iron’s main benefits?

Iron supplements should be used cautiously, only when required, and in accordance with recommended doses. Prolonged use of iron supplements or an excess of iron in the system can lead to adverse side effects.
Iron supplements frequently result in gastrointestinal discomfort, including symptoms such as <a href="/outcomes/nausea-symptoms/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Nausea Symptoms&lt;/h6&gt;&lt;p&gt;Nausea is the feeling of acute sickness that may result in vomiting and loss of appetite. Some supplements are known as antiemetics, and are used to reduce the sensation of nausea when taken.&lt;/p&gt;&lt;/div&gt;">nausea</a>, <a href="/outcomes/abdominal-pain/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Abdominal Pain&lt;/h6&gt;&lt;p&gt;Abdominal pain is a pain that originates within the abdomen. It can occur due to a variety of factors that may be benign such as indigestion or more serious conditions such as colon cancer.&lt;/p&gt;&lt;/div&gt;">abdominal pain</a>, dark stool, <a href="/outcomes/heartburn-symptoms/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Heartburn Symptoms&lt;/h6&gt;&lt;p&gt;Heartburn is a painful sensation felt in the chest due to stomach acid traveling up into the esophagus. Symptoms are usually worse after eating, lying down, or bending over.&lt;/p&gt;&lt;/div&gt;">heartburn</a>, and <a href="/conditions/constipation/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Constipation&lt;/h6&gt;&lt;p&gt;Constipation occurs when the process of defecation is impaired to such a degree that a person can no longer easily pass stool.&lt;/p&gt;&lt;/div&gt;">constipation</a>, and other side effects such as <a href="/outcomes/headaches/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Headaches&lt;/h6&gt;&lt;p&gt;Headaches are characterized by pain throughout the head and/or face. The location, intensity, and causes of headaches can vary.&lt;/p&gt;&lt;/div&gt;">headache</a>. This can be a significant challenge for individuals with IDA, who may find it difficult to adhere to their treatment recommendations.<a href="#ref-12" id="ref-link-12" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Gutema BT, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/37368919" target="\_blank" rel="noopener noreferrer"&gt;Effects of iron supplementation on cognitive development in school-age children: Systematic review and meta-analysis.
&lt;/a&gt;&lt;/p&gt;PLoS One (2023)&lt;/div&gt;'>[12]</a>
Although ferritin, hemosiderin, and transferrin play essential roles in regulating iron levels in the system, an excessive amount of free iron can trigger the production of free radicals and increase oxidative stress. This can potentially lead to damage to proteins and cells, and harm the body.<a href="#ref-15" id="ref-link-15" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Deli C. K., et al. &lt;a href="https://www.intechopen.com/chapters/44692" target="\_blank" rel="noopener noreferrer"&gt;Iron Supplementation and Physical Performance
&lt;/a&gt;&lt;/p&gt;Current Issues in Sports and Exercise Medicine (2013 May)&lt;/div&gt;'>[15]</a><a href="#ref-16" id="ref-link-16" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Brissot P, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/21855608" target="\_blank" rel="noopener noreferrer"&gt;Non-transferrin bound iron: a key role in iron overload and iron toxicity
&lt;/a&gt;&lt;/p&gt;Biochim Biophys Acta (2012 Mar)&lt;/div&gt;'>[16]</a> Diseases characterized by iron overload include hemochromatosis, a hereditary disease in which iron builds up to toxic levels in the body, which can lead to damage to organs such as liver, joints pancreas or heart.<a href="#ref-17" id="ref-link-17" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Charlebois E, Pantopoulos K. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/37299408" target="\_blank" rel="noopener noreferrer"&gt;Nutritional Aspects of Iron in Health and Disease.
&lt;/a&gt;&lt;/p&gt;Nutrients (2023-May-24)&lt;/div&gt;'>[17]</a>
Additionally, multiple observational studies have reported that regular consumption of dietary iron, especially heme iron sourced from meat products, may predispose one to numerous diseases (e.g., <a href="/conditions/type-2-diabetes/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Type 2 Diabetes&lt;/h6&gt;&lt;p&gt;Type 2 diabetes (T2D) is a disease in which blood glucose levels are too high. It is characterized by insulin resistance in muscle, fat, and pancreas cells and an inability of the pancreas to manufacture enough insulin to control blood glucose levels. T2D is strongly associated with excess body fat, and weight loss induced by lifestyle changes is extremely effective for treating T2D.&lt;/p&gt;&lt;/div&gt;">type 2 diabetes</a>, <a href="/conditions/cardiovascular-disease/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Cardiovascular Disease&lt;/h6&gt;&lt;p&gt;Cardiovascular disease (CVD) is a broad term that refers to various diseases of the heart and blood vessels. Atherosclerotic CVD (ASCVD) is the most common subtype of CVD and causes strokes and heart attacks.&lt;/p&gt;&lt;/div&gt;">cardiovascular disease</a>, coronary heart disease) and may increase the risk of some cancers (e.g., <a href="/conditions/breast-cancer/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Breast Cancer&lt;/h6&gt;&lt;p&gt;Breast cancer is the second most common cancer in women, after skin cancer. It affects men very rarely. It is most treatable when caught early, therefore it is important to do regular breast exams and regular physician visits.&lt;/p&gt;&lt;/div&gt;">breast</a>, <a href="/conditions/colorectal-cancer/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Colorectal Cancer&lt;/h6&gt;&lt;p&gt;&lt;em&gt;Colorectal cancer&lt;/em&gt; (CRC) occurs when tumors form in the lining of the colon or rectum (which together make up the large intestine). Symptoms include a change in bowel habits, fatigue, and unexplained weight loss. CRC is diagnosed after a physical exam of the colon and rectum. It can be treated in a variety of ways, including surgery, immunotherapy, and chemotherapy.&lt;/p&gt;&lt;/div&gt;">colorectal</a>, and <a href="/conditions/esophageal-cancer/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Esophageal Cancer&lt;/h6&gt;&lt;p&gt;Esophageal cancer is characterized by abnormal cell growth and replication in the esophagus, a hollow, muscular tube that connects the throat to the stomach.&lt;/p&gt;&lt;/div&gt;">esophageal cancer</a>). However, the majority of these claims are based on self-reported food diaries or food questionnaires, and the level of evidence is weak. Furthermore, it’s important to highlight that processed meat does not only contain heme iron, but other potentially harmful substances (e.g., nitrite, nitrate, heterocyclic amines) which may be confounding factors that also raise the risk of some diseases.<a href="#ref-17" id="ref-link-17" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Charlebois E, Pantopoulos K. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/37299408" target="\_blank" rel="noopener noreferrer"&gt;Nutritional Aspects of Iron in Health and Disease.
&lt;/a&gt;&lt;/p&gt;Nutrients (2023-May-24)&lt;/div&gt;'>[17]</a>
In children, low doses of iron may cause diarrhea, but they do not appear to increase the risk of infections at the recommended dosage. Nevertheless, the World Health Organization (WHO) advises monitoring children in countries at high risk of malaria when receiving iron supplementation, as it may both increase the risk of contracting the disease and potentially worsen its effects. The mechanism by which iron interacts with malaria is still not fully understood.<a href="#ref-12" id="ref-link-12" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Gutema BT, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/37368919" target="\_blank" rel="noopener noreferrer"&gt;Effects of iron supplementation on cognitive development in school-age children: Systematic review and meta-analysis.
&lt;/a&gt;&lt;/p&gt;PLoS One (2023)&lt;/div&gt;'>[12]</a><a href="#ref-18" id="ref-link-18" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Fernández-Gaxiola AC, De-Regil LM. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/30699468" target="\_blank" rel="noopener noreferrer"&gt;Intermittent iron supplementation for reducing anaemia and its associated impairments in adolescent and adult menstruating women
&lt;/a&gt;&lt;/p&gt;Cochrane Database Syst Rev (2019 Jan 31)&lt;/div&gt;'>[18]</a>

What are iron’s main drawbacks?

Heme iron is more readily absorbed compared to non-heme iron, but the bioavailability of iron in the body can be influenced by several foods and dietary components. In individuals following a mixed diet, which includes fruit, vegetables, meat, and seafood, the bioavailability of iron ranges from approximately 14% to 18%. For vegetarian diets, iron bioavailability can range from 5% to 12%.<a href="#ref-1" id="ref-link-1" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;&lt;a href="https://ods.od.nih.gov/factsheets/iron-HealthProfessional/" target="\_blank" rel="noopener noreferrer"&gt;Iron Fact Sheet for Health Professionals. MedlinePlus. National Institutes of Health (NIH) Office of Dietary Supplements (ODS). Updated 2023 Jun 15; cited 2023 December 5
&lt;/a&gt;&lt;/p&gt;&lt;/div&gt;'>[1]</a>
Animal protein appears to increase non-heme iron absorption from non-meat produce (e.g., vegetables, grains) when these foods are consumed in the same meal. However, this effect was less pronounced for wheat than for other plant-based foods.<a href="#ref-29" id="ref-link-29" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Lynch SR, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/2658489" target="\_blank" rel="noopener noreferrer"&gt;The effect of dietary proteins on iron bioavailability in man
&lt;/a&gt;&lt;/p&gt;Adv Exp Med Biol (1989)&lt;/div&gt;'>[29]</a><a href="#ref-30" id="ref-link-30" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Reddy MB, Hurrell RF, Cook JD. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/16484527" target="\_blank" rel="noopener noreferrer"&gt;Meat consumption in a varied diet marginally influences nonheme iron absorption in normal individuals
&lt;/a&gt;&lt;/p&gt;J Nutr (2006 Mar)&lt;/div&gt;'>[30]</a> Additionally, studies have yielded mixed results regarding the combination of pork meat with meals high in phytates (which can be found in certain legumes and vegetables), indicating that phytate may counteract the positive effects of animal protein on non-heme iron absorption.<a href="#ref-31" id="ref-link-31" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Bach Kristensen M, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/16115336" target="\_blank" rel="noopener noreferrer"&gt;Pork meat increases iron absorption from a 5-day fully controlled diet when compared to a vegetarian diet with similar vitamin C and phytic acid content
&lt;/a&gt;&lt;/p&gt;Br J Nutr (2005 Jul)&lt;/div&gt;'>[31]</a><a href="#ref-32" id="ref-link-32" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Baech SB, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/12499338" target="\_blank" rel="noopener noreferrer"&gt;Nonheme-iron absorption from a phytate-rich meal is increased by the addition of small amounts of pork meat
&lt;/a&gt;&lt;/p&gt;Am J Clin Nutr (2003 Jan)&lt;/div&gt;'>[32]</a>
It’s often recommended that iron be taken with <a href="/supplements/vitamin-c/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Vitamin C&lt;/h6&gt;&lt;p&gt;Vitamin C, or ascorbic acid, is an essential vitamin and a very popular supplement due to its antioxidant properties, safety profile, and low price. Many people supplement with vitamin C because it is believed to reduce symptoms of the common cold.&lt;/p&gt;&lt;/div&gt;">Vitamin C</a> (ascorbic acid) supplements or vitamin C-rich foods. Theoretically, ascorbic acid can facilitate the reduction of ferric iron to its more bioavailable form (ferrous iron), and can chelate iron ions (i.e., bond with them) to enhance their solubility and absorption from the intestines into the bloodstream.<a href="#ref-33" id="ref-link-33" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Loganathan V, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/37739692" target="\_blank" rel="noopener noreferrer"&gt;Treatment efficacy of vitamin C or ascorbate given as co-intervention with iron for anemia - A systematic review and meta-analysis of experimental studies.
&lt;/a&gt;&lt;/p&gt;Clin Nutr ESPEN (2023-Oct)&lt;/div&gt;'>[33]</a> Furthermore, ascorbate (a mineral salt of ascorbic acid) regulates the uptake of iron by transferrin, which is why scurvy (a disease resulting from a vitamin C deficiency) is often associated with some degree of iron-deficiency anemia.<a href="#ref-34" id="ref-link-34" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Lane DJ, Richardson DR. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/25048971" target="\_blank" rel="noopener noreferrer"&gt;The active role of vitamin C in mammalian iron metabolism: much more than just enhanced iron absorption!
&lt;/a&gt;&lt;/p&gt;Free Radic Biol Med (2014-Oct)&lt;/div&gt;'>[34]</a> However, two meta-analyses both found no difference in hemoglobin and ferritin levels when iron was supplemented with vitamin C, compared to iron alone,<a href="#ref-33" id="ref-link-33" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Loganathan V, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/37739692" target="\_blank" rel="noopener noreferrer"&gt;Treatment efficacy of vitamin C or ascorbate given as co-intervention with iron for anemia - A systematic review and meta-analysis of experimental studies.
&lt;/a&gt;&lt;/p&gt;Clin Nutr ESPEN (2023-Oct)&lt;/div&gt;'>[33]</a><a href="#ref-35" id="ref-link-35" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Duarte AFM, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/34784635" target="\_blank" rel="noopener noreferrer"&gt;Oral Iron Supplementation in Pregnancy: Current Recommendations and Evidence-Based Medicine.
&lt;/a&gt;&lt;/p&gt;Rev Bras Ginecol Obstet (2021-Oct)&lt;/div&gt;'>[35]</a> suggesting that there is still limited clinical data on the benefits of combining iron and vitamin C.

Which foods or supplements enhance iron absorption?

Iron absorption can be reduced by other vitamins and minerals found both in supplements and foods.
Multiple studies have found that <a href="/supplements/calcium/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Calcium&lt;/h6&gt;&lt;p&gt;Calcium is a dietary macromineral found in high amounts in dairy products, and to a lesser extent in vegetables. Used primarily to support bone health, calcium also has a role in maternal and cardiovascular health.&lt;/p&gt;&lt;/div&gt;">calcium</a> is a strong inhibitor of iron absorption, and avoiding the simultaneous use of calcium and iron supplements may be beneficial. In one study, calcium phosphate inhibited iron absorption from a ferrous sulfate supplement, whether taken with or without food. In contrast, calcium carbonate only inhibited iron absorption when both supplements were consumed with food, suggesting that if a combined iron and calcium carbonate supplement is required, it should be taken between meals.<a href="#ref-36" id="ref-link-36" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Cook JD, Dassenko SA, Whittaker P. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/1984334" target="\_blank" rel="noopener noreferrer"&gt;Calcium supplementation: effect on iron absorption
&lt;/a&gt;&lt;/p&gt;Am J Clin Nutr (1991 Jan)&lt;/div&gt;'>[36]</a> Calcium citrate, on the other hand, reduced iron absorption both with and without food, but not to a statistically significant degree in one study<a href="#ref-36" id="ref-link-36" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Cook JD, Dassenko SA, Whittaker P. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/1984334" target="\_blank" rel="noopener noreferrer"&gt;Calcium supplementation: effect on iron absorption
&lt;/a&gt;&lt;/p&gt;Am J Clin Nutr (1991 Jan)&lt;/div&gt;'>[36]</a>, and reduced absorption of non-heme iron without food in another study.<a href="#ref-37" id="ref-link-37" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Candia V, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/29895376" target="\_blank" rel="noopener noreferrer"&gt;Effect of various calcium salts on non-heme iron bioavailability in fasted women of childbearing age
&lt;/a&gt;&lt;/p&gt;J Trace Elem Med Biol (2018 Sep)&lt;/div&gt;'>[37]</a>. The impact of calcium chloride on iron absorption seems to vary depending on whether it’s taken with food<a href="#ref-38" id="ref-link-38" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Hallberg L, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/1984335" target="\_blank" rel="noopener noreferrer"&gt;Calcium: effect of different amounts on nonheme- and heme-iron absorption in humans
&lt;/a&gt;&lt;/p&gt;Am J Clin Nutr (1991 Jan)&lt;/div&gt;'>[38]</a> or without food.<a href="#ref-39" id="ref-link-39" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Gaitán D, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/21795430" target="\_blank" rel="noopener noreferrer"&gt;Calcium does not inhibit the absorption of 5 milligrams of nonheme or heme iron at doses less than 800 milligrams in nonpregnant women
&lt;/a&gt;&lt;/p&gt;J Nutr (2011 Sep)&lt;/div&gt;'>[39]</a>
Furthermore, a wide variety of beverages with a high antioxidant content, including coffee and tea, have some acute inhibitory effects on non-heme iron absorption. <a href="/foods/coffee/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Coffee&lt;/h6&gt;&lt;p&gt;Sometimes referred to as liquid gold, coffee is the most popular source of caffeine in North America (and behind only teas worldwide). Also a source of tons of nutrients, and most recently touted as a source of chlorogenic acid and ferulic acid.&lt;/p&gt;&lt;/div&gt;">Coffee</a> may reduce iron absorption,<a href="#ref-40" id="ref-link-40" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;R F Hurrell, M Reddy, J D Cook. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/10999016" target="\_blank" rel="noopener noreferrer"&gt;Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages
&lt;/a&gt;&lt;/p&gt;Br J Nutr (1999 Apr)&lt;/div&gt;'>[40]</a> possibly due to the presence of <a href="/supplements/chlorogenic-acid/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Chlorogenic Acid&lt;/h6&gt;&lt;p&gt;Chlorogenic acid is found in coffee mostly and a lot of plant compounds; it holds promise in many aspects of health and cognition similar to bioflavonoids and shares some effects similar to caffeine but less potent. May decrease the absorption of dietary carbohydrate.&lt;/p&gt;&lt;/div&gt;">chlorogenic acid</a>, a known iron chelator.<a href="#ref-41" id="ref-link-41" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Kono Y, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/9501514" target="\_blank" rel="noopener noreferrer"&gt;Iron chelation by chlorogenic acid as a natural antioxidant.
&lt;/a&gt;&lt;/p&gt;Biosci Biotechnol Biochem (1998-Jan)&lt;/div&gt;'>[41]</a> This mechanism can be extended to green coffee extract, which is an even richer source of chlorogenic acid. Tea, whether <a href="/foods/green-tea/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Green Tea&lt;/h6&gt;&lt;p&gt;Green tea contains more antioxidants and polyphenols than any other tea variety. It is a major source of the compound &lt;em&gt;epigallocatechin gallate&lt;/em&gt; (EGCG). Green tea is widely used in traditional Chinese medicine and has been linked to a reduced risk for several major diseases. &lt;em&gt;Green Tea Extract&lt;/em&gt; is a common supplement.&lt;/p&gt;&lt;/div&gt;">green</a><a href="#ref-42" id="ref-link-42" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Samman S, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/11237939" target="\_blank" rel="noopener noreferrer"&gt;Green tea or rosemary extract added to foods reduces nonheme-iron absorption.
&lt;/a&gt;&lt;/p&gt;Am J Clin Nutr (2001-Mar)&lt;/div&gt;'>[42]</a> or black,<a href="#ref-40" id="ref-link-40" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;R F Hurrell, M Reddy, J D Cook. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/10999016" target="\_blank" rel="noopener noreferrer"&gt;Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages
&lt;/a&gt;&lt;/p&gt;Br J Nutr (1999 Apr)&lt;/div&gt;'>[40]</a> might inhibit iron absorption, possibly due to the presence of catechins<a href="#ref-42" id="ref-link-42" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Samman S, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/11237939" target="\_blank" rel="noopener noreferrer"&gt;Green tea or rosemary extract added to foods reduces nonheme-iron absorption.
&lt;/a&gt;&lt;/p&gt;Am J Clin Nutr (2001-Mar)&lt;/div&gt;'>[42]</a> and <a href="/supplements/theaflavins/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Theaflavins&lt;/h6&gt;&lt;p&gt;Theaflavins are a group of molecules that are found in black tea (due to an additional fermentation process from green tea) that are said to be the bioactives of black tea.&lt;/p&gt;&lt;/div&gt;">theaflavins</a>.<a href="#ref-43" id="ref-link-43" class="ref-link popover" data-tooltip="&lt;div&gt;&lt;p class=&quot;mb-3&quot;&gt;O'Coinceanainn M, et al. &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15041246&quot; target=&quot;\_blank&quot; rel=&quot;noopener noreferrer&quot;&gt;Reaction of iron(III) with theaflavin: complexation and oxidative products.
&lt;/a&gt;&lt;/p&gt;J Inorg Biochem (2004-Apr)&lt;/div&gt;">[43]</a>
Infusions of <a href="/foods/chamomile/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Chamomile&lt;/h6&gt;&lt;p&gt;Chamomile is commonly consumed as an herbal tea or used as an essential oil in aromatherapy. Due to the high amounts of terpenes and flavonoids in chamomile, it has been used to treat anxiety, gastrointestinal disorders, inflammation, and insomnia.&lt;/p&gt;&lt;/div&gt;">chamomile</a>, lime flower, pennyroyal, peppermint, and vervain may also reduce non-heme iron absorption.<a href="#ref-40" id="ref-link-40" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;R F Hurrell, M Reddy, J D Cook. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/10999016" target="\_blank" rel="noopener noreferrer"&gt;Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages
&lt;/a&gt;&lt;/p&gt;Br J Nutr (1999 Apr)&lt;/div&gt;'>[40]</a>
Rosemary (a source of rosmarinic acid), rich in phytic and phenolic acid, has also been shown to reduce non-heme iron absorption.<a href="#ref-42" id="ref-link-42" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Samman S, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/11237939" target="\_blank" rel="noopener noreferrer"&gt;Green tea or rosemary extract added to foods reduces nonheme-iron absorption.
&lt;/a&gt;&lt;/p&gt;Am J Clin Nutr (2001-Mar)&lt;/div&gt;'>[42]</a>
Additionally, in one randomized controlled trial, people with beta-thalassemia who took 500 mg of <a href="/supplements/quercetin/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Quercetin&lt;/h6&gt;&lt;p&gt;Quercetin is the most well researched of all bioflavonoids. It is not actually that good of a supplement on its own, but is an interesting research topic. Tons of interactions, and synergistic with other bioflavonoids and increases absorption of Resveratrol and Green Tea Catechins.&lt;/p&gt;&lt;/div&gt;">quercetin</a> (a chelator of iron<a href="#ref-44" id="ref-link-44" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Leopoldini M, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/16910729" target="\_blank" rel="noopener noreferrer"&gt;Iron chelation by the powerful antioxidant flavonoid quercetin
&lt;/a&gt;&lt;/p&gt;J Agric Food Chem (2006 Aug 23)&lt;/div&gt;'>[44]</a>) per day for 12 weeks alleviated iron overload (a common complication of beta-thalassemia), notably reducing serum iron, ferritin, and inflammatory markers.<a href="#ref-45" id="ref-link-45" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Sajadi Hezaveh Z, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/31519283" target="\_blank" rel="noopener noreferrer"&gt;The effect of quercetin on iron overload and inflammation in β-thalassemia major patients: A double-blind randomized clinical trial
&lt;/a&gt;&lt;/p&gt;Complement Ther Med (2019 Oct)&lt;/div&gt;'>[45]</a>
Lastly, although <a href="/supplements/zinc/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Zinc&lt;/h6&gt;&lt;p&gt;Zinc is an essential mineral that is critical for the function of hundreds of enzymes. Consequently, it plays many roles, including in antioxidant enzymes, brain function, and the immune system. Zinc is most commonly taken to reduce the duration of respiratory infections and the common cold.&lt;/p&gt;&lt;/div&gt;">zinc</a> has the potential to reduce the absorption of iron, the effect is inconsistent, and the strength of this effect is unclear, with different studies reporting varying results.<a href="#ref-13" id="ref-link-13" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Andersen CT, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/36849195" target="\_blank" rel="noopener noreferrer"&gt;Oral iron supplementation and anaemia in children according to schedule, duration, dose and cosupplementation: a systematic review and meta-analysis of 129 randomised trials.
&lt;/a&gt;&lt;/p&gt;BMJ Glob Health (2023-Feb)&lt;/div&gt;'>[13]</a><a href="#ref-46" id="ref-link-46" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Olivares M, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/22297381" target="\_blank" rel="noopener noreferrer"&gt;Acute inhibition of iron bioavailability by zinc: studies in humans
&lt;/a&gt;&lt;/p&gt;Biometals (2012 Aug)&lt;/div&gt;'>[46]</a><a href="#ref-47" id="ref-link-47" class="ref-link popover" data-tooltip="&lt;div&gt;&lt;p class=&quot;mb-3&quot;&gt;O'Brien KO, et al. &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10075338&quot; target=&quot;\_blank&quot; rel=&quot;noopener noreferrer&quot;&gt;Influence of prenatal iron and zinc supplements on supplemental iron absorption, red blood cell iron incorporation, and iron status in pregnant Peruvian women
&lt;/a&gt;&lt;/p&gt;Am J Clin Nutr (1999 Mar)&lt;/div&gt;">[47]</a><a href="#ref-48" id="ref-link-48" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Nguyen P, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/22720141" target="\_blank" rel="noopener noreferrer"&gt;Effect of zinc on efficacy of iron supplementation in improving iron and zinc status in women
&lt;/a&gt;&lt;/p&gt;J Nutr Metab (2012)&lt;/div&gt;'>[48]</a><a href="#ref-49" id="ref-link-49" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;de Brito NJ, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/25192026" target="\_blank" rel="noopener noreferrer"&gt;Oral zinc supplementation decreases the serum iron concentration in healthy schoolchildren: a pilot study
&lt;/a&gt;&lt;/p&gt;Nutrients (2014 Sep 4)&lt;/div&gt;'>[49]</a> The interaction between zinc and iron seems to be linked to competition for transporters in the liver, such as divalent metal transporter 1 (DMT1), human copper transporter 1 (hCTR1),<a href="#ref-50" id="ref-link-50" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Espinoza A, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/22068728" target="\_blank" rel="noopener noreferrer"&gt;Iron, copper, and zinc transport: inhibition of divalent metal transporter 1 (DMT1) and human copper transporter 1 (hCTR1) by shRNA
&lt;/a&gt;&lt;/p&gt;Biol Trace Elem Res (2012 May)&lt;/div&gt;'>[50]</a> and ZRT/IRT-like protein 14 (Zip14).<a href="#ref-51" id="ref-link-51" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Liuzzi JP, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/16950869" target="\_blank" rel="noopener noreferrer"&gt;Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells
&lt;/a&gt;&lt;/p&gt;Proc Natl Acad Sci U S A (2006 Sep 12)&lt;/div&gt;'>[51]</a> Taking zinc between meals is likely a good way to prevent any interference with iron absorption.
It’s important to note that the typical Western diet is complex and rich in both iron absorption enhancers and inhibitors, whose effects may both be attenuated when these substances are consumed simultaneously.<a href="#ref-1" id="ref-link-1" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;&lt;a href="https://ods.od.nih.gov/factsheets/iron-HealthProfessional/" target="\_blank" rel="noopener noreferrer"&gt;Iron Fact Sheet for Health Professionals. MedlinePlus. National Institutes of Health (NIH) Office of Dietary Supplements (ODS). Updated 2023 Jun 15; cited 2023 December 5
&lt;/a&gt;&lt;/p&gt;&lt;/div&gt;'>[1]</a>

Which foods or supplements decrease iron absorption?

Iron supplementation is often associated with gastrointestinal side effects, which may impact treatment adherence. As a result, researchers have explored different dosages and frequencies of supplementation.
One meta-analysis looked at intermittent (once, twice, or three times per week) iron supplementation vs. daily supplementation for improving iron status and preventing anemia in menstruating adolescent and adult women. Both had similar effects on hemoglobin levels and the risk of anemia. However, daily supplementation proved more effective in increasing ferritin levels (although with low quality of evidence), which may be especially significant in populations with a high prevalence of ID, which is characterized by adequate levels of hemoglobin but low ferritin and/or transferrin saturation.<a href="#ref-55" id="ref-link-55" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Al-Nassem, A. et al. &lt;a href="https://doi.org/10.7861/clinmed.2020-0582" target="\_blank" rel="noopener noreferrer"&gt;Iron deficiency without anemia: a diagnosis that matters
&lt;/a&gt;&lt;/p&gt;Clin Med &lt;/div&gt;'>[55]</a> Moreover, there were no significant differences in treatment adherence or in the side effects experienced among participants in the two groups.<a href="#ref-18" id="ref-link-18" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Fernández-Gaxiola AC, De-Regil LM. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/30699468" target="\_blank" rel="noopener noreferrer"&gt;Intermittent iron supplementation for reducing anaemia and its associated impairments in adolescent and adult menstruating women
&lt;/a&gt;&lt;/p&gt;Cochrane Database Syst Rev (2019 Jan 31)&lt;/div&gt;'>[18]</a> There is currently no evidence that intermittent supplementation offers advantages in terms of fewer side effects or improved adherence compared to daily supplementation.
In another study, iron-depleted (but not deficient) participants took the same iron dose either daily or on alternate days for 14 and 28 days, respectively. The alternate-day dosing regimen resulted in reduced levels of hepcidin (a hormone responsible for regulating iron homeostasis in the body) and greater iron absorption. However, the impact on iron status remained unclear because there were no notable differences in serum iron, ferritin, or hemoglobin levels between the two groups at the end of the trial. Additionally, the alternate-day dosing group reported experiencing less nausea but more headaches.<a href="#ref-56" id="ref-link-56" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Stoffel NU, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/29032957" target="\_blank" rel="noopener noreferrer"&gt;Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials
&lt;/a&gt;&lt;/p&gt;Lancet Haematol (2017 Nov)&lt;/div&gt;'>[56]</a> A subsequent study by the same author, including individuals with ID, confirmed these findings. However, the study’s duration was too short to assess the long-term effects on iron status.<a href="#ref-57" id="ref-link-57" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Stoffel NU, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/31413088" target="\_blank" rel="noopener noreferrer"&gt;Iron absorption from supplements is greater with alternate day than with consecutive day dosing in iron-deficient anemic women
&lt;/a&gt;&lt;/p&gt;Haematologica (2019 Aug 14)&lt;/div&gt;'>[57]</a>

Is intermittent or alternate-day iron supplementation more effective than daily supplementation?

Understanding the process of iron absorption in the body is key to grasping its mechanism of action. The disparity in absorption between heme and non-heme iron has implications for the amount of elemental iron absorbed in the body, with heme iron, typically found in animal products, being absorbed more efficiently.<a href="#ref-19" id="ref-link-19" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Carpenter CE, Mahoney AW. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/1581009" target="\_blank" rel="noopener noreferrer"&gt;Contributions of heme and nonheme iron to human nutrition
&lt;/a&gt;&lt;/p&gt;Crit Rev Food Sci Nutr (1992)&lt;/div&gt;'>[19]</a>
Both heme and non-heme iron are primarily absorbed in the duodenum and, to a lesser extent, in the upper jejunum (the first and second sections of the small intestine, respectively). Heme iron enters the gastrointestinal tract as ferrous iron (i.e., with a 2+ oxidation state), which is more easily absorbed, while non-heme iron is typically ingested in its ferric (3+) form. However, for non-heme iron to be absorbed, it must first be reduced into ferrous iron by reductase enzymes (e.g., ascorbate ferrireductase), or other compounds like vitamin C. Ferrous iron is then taken up by enterocytes lining the intestine through the divalent metal transporter 1 (DMT1), and then leaves these cells and enters the bloodstream via ferroportin. Once in the bloodstream, iron is converted back from ferrous to ferric iron and transported by transferrin to various organs and tissues.<a href="#ref-20" id="ref-link-20" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Sharp P, Srai SK. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/17729393" target="\_blank" rel="noopener noreferrer"&gt;Molecular mechanisms involved in intestinal iron absorption
&lt;/a&gt;&lt;/p&gt;World J Gastroenterol (2007 Sep 21)&lt;/div&gt;'>[20]</a>
After absorption, iron plays a crucial role in several reactions and biological processes within the body, many of which are centered around iron’s roles in protein function and oxygen transport and storage. Iron is required to form hemoglobin (an oxygen-transporter protein) and myoglobin (an oxygen-storage protein). Inadequate iron intake can hinder the production of healthy red blood cells, potentially leading to anemia. In mitochondria, iron serves as a cofactor in proteins that contain iron-sulfur clusters (e.g., flavoproteins), other heme-containing proteins involved in the electron transport chain (e.g., cytochrome c oxidase), and proteins that contain iron ions (e.g., monooxygenases and dioxygenases).<a href="#ref-21" id="ref-link-21" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Paul BT, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/27911100" target="\_blank" rel="noopener noreferrer"&gt;Mitochondria and Iron: current questions.
&lt;/a&gt;&lt;/p&gt;Expert Rev Hematol (2017-Jan)&lt;/div&gt;'>[21]</a><a href="#ref-10" id="ref-link-10" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Hamed M, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/37383191" target="\_blank" rel="noopener noreferrer"&gt;Intravenous iron therapy among patients with heart failure and iron deficiency: An updated meta-analysis of randomized controlled trials.
&lt;/a&gt;&lt;/p&gt;Heliyon (2023-Jun)&lt;/div&gt;'>[10]</a> Additionally, iron is involved in cell growth and differentiation, electron transfer reactions for energy production, and the regulation of the expression of some genes.<a href="#ref-15" id="ref-link-15" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Deli C. K., et al. &lt;a href="https://www.intechopen.com/chapters/44692" target="\_blank" rel="noopener noreferrer"&gt;Iron Supplementation and Physical Performance
&lt;/a&gt;&lt;/p&gt;Current Issues in Sports and Exercise Medicine (2013 May)&lt;/div&gt;'>[15]</a>
Iron is also an essential nutrient for brain development and function. It plays a role in energy (ATP) production and neurotransmitter synthesis, as well as in the uptake and degradation of neurotransmitters, all of which are involved in behavior, <a href="/outcomes/memory/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Memory&lt;/h6&gt;&lt;p&gt;The ability to store and recall information. Memory-boosting supplements have mostly been tested in older people, whose memory has degraded, but this page deals with any form of memory and any study population.&lt;/p&gt;&lt;/div&gt;">memory</a>, learning, and sensory systems.<a href="#ref-12" id="ref-link-12" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Gutema BT, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/37368919" target="\_blank" rel="noopener noreferrer"&gt;Effects of iron supplementation on cognitive development in school-age children: Systematic review and meta-analysis.
&lt;/a&gt;&lt;/p&gt;PLoS One (2023)&lt;/div&gt;'>[12]</a><a href="#ref-22" id="ref-link-22" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Chen Z, et al. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/36558491" target="\_blank" rel="noopener noreferrer"&gt;Effect of Oral Iron Supplementation on Cognitive Function among Children and Adolescents in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.
&lt;/a&gt;&lt;/p&gt;Nutrients (2022-Dec-15)&lt;/div&gt;'>[22]</a> 
It’s important to note that when iron supplements are taken to treat IDA, it usually takes about 3 months to replenish iron stores, and hemoglobin levels will increase gradually in the first month of supplementation.<a href="#ref-23" id="ref-link-23" class="ref-link popover" data-tooltip='&lt;div&gt;&lt;p class="mb-3"&gt;Arulparithi CS, Arunbabu T, Manjani S. &lt;a href="https://pubmed.ncbi.nlm.nih.gov/37209050" target="\_blank" rel="noopener noreferrer"&gt;Iron Preparations in the Management of Iron Deficiency Anemia in Infants and Children: A Systematic Review and Meta-Analysis.
&lt;/a&gt;&lt;/p&gt;Indian Pediatr (2023-Sep-15)&lt;/div&gt;'>[23]</a>

How does iron work?

Iron

Cast iron pans are popular, especially for searing, and are generally safe to use. But they can leach iron, which is a strong pro-oxidant. Those genetically at risk for iron overload should learn more about cast iron safety.

Are cast iron pans unsafe?

Women’s Health

Iron Fact Sheet for Health Professionals. MedlinePlus. National Institutes of Health (NIH) Office of Dietary Supplements (ODS). Updated 2023 Jun 15; cited 2023 December 5

Diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0-3 years of age).

Diagnosis and Prevention of Iron Deficiency and Iron-Deficiency Anemia in Infants and Young Children (0–3 Years of Age)

Iron Deficiency Anemia in Infancy, Childhood, and Adolescence.

Iron-sulfur cluster biosynthesis.

Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Chapter 9, Iron

Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials

Role of iron in the reduction of anemia among women of reproductive age in low-middle income countries: insights from systematic review and meta-analysis.

Iron supplements in pregnant women with normal iron status: A systematic review and meta-analysis.

Intravenous iron therapy among patients with heart failure and iron deficiency: An updated meta-analysis of randomized controlled trials.

Meta-Analysis of Efficacy and Safety of Intravenous Iron in Patients With Iron Deficiency and Heart Failure With Reduced Ejection Fraction.

Effects of iron supplementation on cognitive development in school-age children: Systematic review and meta-analysis.

Oral iron supplementation and anaemia in children according to schedule, duration, dose and cosupplementation: a systematic review and meta-analysis of 129 randomised trials.

Iron supplementation for restless legs syndrome - A systematic review and meta-analysis

Iron Supplementation and Physical Performance

Non-transferrin bound iron: a key role in iron overload and iron toxicity

Nutritional Aspects of Iron in Health and Disease.

Intermittent iron supplementation for reducing anaemia and its associated impairments in adolescent and adult menstruating women

Contributions of heme and nonheme iron to human nutrition

Molecular mechanisms involved in intestinal iron absorption

Mitochondria and Iron: current questions.

Effect of Oral Iron Supplementation on Cognitive Function among Children and Adolescents in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.

Iron Preparations in the Management of Iron Deficiency Anemia in Infants and Children: A Systematic Review and Meta-Analysis.

The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials.

Production and Characterization of Heme Iron Polypeptide from the Blood of Skipjack Tuna () Using Enzymatic Hydrolysis for Food Supplement Application.

Clinical studies of hip: An oral heme-iron product

Iron preparations for women of reproductive age with iron deficiency anaemia in pregnancy (FRIDA): a systematic review and network meta-analysis.

Comparison study of oral iron preparations using a human intestinal model.

The effect of dietary proteins on iron bioavailability in man

Meat consumption in a varied diet marginally influences nonheme iron absorption in normal individuals

Pork meat increases iron absorption from a 5-day fully controlled diet when compared to a vegetarian diet with similar vitamin C and phytic acid content

Nonheme-iron absorption from a phytate-rich meal is increased by the addition of small amounts of pork meat

Treatment efficacy of vitamin C or ascorbate given as co-intervention with iron for anemia - A systematic review and meta-analysis of experimental studies.

The active role of vitamin C in mammalian iron metabolism: much more than just enhanced iron absorption!

Oral Iron Supplementation in Pregnancy: Current Recommendations and Evidence-Based Medicine.

Calcium supplementation: effect on iron absorption

Effect of various calcium salts on non-heme iron bioavailability in fasted women of childbearing age

Calcium: effect of different amounts on nonheme- and heme-iron absorption in humans

Calcium does not inhibit the absorption of 5 milligrams of nonheme or heme iron at doses less than 800 milligrams in nonpregnant women

Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages

Iron chelation by chlorogenic acid as a natural antioxidant.

Green tea or rosemary extract added to foods reduces nonheme-iron absorption.

Reaction of iron(III) with theaflavin: complexation and oxidative products.

Iron chelation by the powerful antioxidant flavonoid quercetin

The effect of quercetin on iron overload and inflammation in β-thalassemia major patients: A double-blind randomized clinical trial

Acute inhibition of iron bioavailability by zinc: studies in humans

Influence of prenatal iron and zinc supplements on supplemental iron absorption, red blood cell iron incorporation, and iron status in pregnant Peruvian women

Effect of zinc on efficacy of iron supplementation in improving iron and zinc status in women

Oral zinc supplementation decreases the serum iron concentration in healthy schoolchildren: a pilot study

Iron, copper, and zinc transport: inhibition of divalent metal transporter 1 (DMT1) and human copper transporter 1 (hCTR1) by shRNA

Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells

Exercise-induced anaemia: a forgotten cause of iron deficiency anaemia in young adults.

Iron stores in professional athletes throughout the sports season.

Effects of iron intake through food or supplement on iron status and performance of healthy adolescent swimmers during a training season.

Iron deficiency without anemia: a diagnosis that matters

Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials

Iron absorption from supplements is greater with alternate day than with consecutive day dosing in iron-deficient anemic women

Influence of blood donation on iron stores assessed by serum ferritin and haemoglobin in a population survey of 1433 Danish males.

A prospective study of blood donations in healthy elderly persons

Worldwide prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System, 1993-2005

Iron deficiency anemia

Iron metabolism, free radicals, and oxidative injury

Iron, free radicals, and oxidative injury

Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson's, Huntington's, Alzheimer's, prions, bactericides, chemical toxicology and others as examples

Dietary intake of heme iron and risk of cardiovascular disease: a dose-response meta-analysis of prospective cohort studies

Intakes of heme iron and zinc and colorectal cancer incidence: a meta-analysis of prospective studies

Pediatric iron poisonings in the United States

Multiple vitamins and vitamins with iron: accidental poisoning in children

Iron absorption and phenolic compounds: importance of different phenolic structures

Iron and blood donation

Reduction of Body Iron in HFE-related Haemochromatosis and Moderate Iron Overload (Mi-Iron): A Multicentre, Participant-Blinded, Randomised Controlled Trial

Metabolic and Hepatic Effects of Bloodletting in Dysmetabolic Iron Overload Syndrome: A Randomized Controlled Study in 274 Patients

An Investigation of the Effects of Curcumin on Iron Overload, Hepcidin Level, and Liver Function in β-Thalassemia Major Patients: A Double-Blind Randomized Controlled Clinical Trial

Iron content of food cooked in iron utensils

Food prepared in iron cooking pots as an intervention for reducing iron deficiency anaemia in developing countries: a systematic review

Effect of consumption of food cooked in iron pots on iron status and growth of young children: a randomised trial

Metal allergy--a review on exposures, penetration, genetics, prevalence, and clinical implications

Stainless steel cookware as a significant source of nickel, chromium, and iron

Identification of carcinogens in cooking oil fumes

Acrylamide in home-prepared roasted potatoes

Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish

Acrylamide in cereal and cereal products: a review on progress in level reduction

PTFE toxicity in birds

Polytetrafluoroethylene fume-induced pulmonary edema: a case report and review of the literature

Nick Milazzo

Natalka Roshak

Giulia Guerrini

Wyatt Brown

Vegetarians & Vegans

Iron Deficiency Anemia

Ferritin

Hemoglobin

Fatigue (non-anemic)

Alertness

Anemia Risk

Depression Symptoms

Iron Deficiency Anemia Risk

Iron Deficiency Risk

Aerobic Exercise Metrics

Memory

Fatigue

Anxiety Symptoms

Exercise Capacity

Diabetes & Blood Sugar

Liver Health

Healthy Aging

Cardiovascular Health

Metabolic Health

Serum Iron

Total Iron Binding Capacity

Transferrin

Heart Failure

Risk of Hospitalization for Heart Failure

6-Minute Walking Test Performance

Left Ventricular Ejection Fraction

Quality of Life

All-Cause Mortality

Cardiovascular Mortality

Pregnancy And Delivery Health

Infant Birth Weight

General Athletic Performance

Muscular Endurance

Oxygen Uptake

Heart Rate

Respiratory Exchange Ratio

Aerobic Exercise Performance

Memory & Focus

Focus & Attention

"Measures of Intelligence
"

Attention

Short-Term Memory (Simple)

Memory Improvement

Fibromyalgia

Fibromyalgia Symptoms

Cognitive Improvement

Infant Health

Low Birth Weight

Menstrual Health

Mood & Depression

Mood Improvement

Muscle Size & Strength

Restless Leg Syndrome

Restless Leg Syndrome Symptoms

Sleep Quality

Running Performance

Randomized, double-blind, placebo-controlled trial of iron supplementation in female soldiers during military training: effects on iron status, physical performance, and mood

Clinical evaluation of iron treatment efficiency among non-anemic but iron-deficient female blood donors: a randomized controlled trial

Evaluation of a single dose of ferric carboxymaltose in fatigued, iron-deficient women--PREFER a randomized, placebo-controlled study

Marginal iron deficiency without anemia impairs aerobic adaptation among previously untrained women

Iron supplementation improves progressive fatigue resistance during dynamic knee extensor exercise in iron-depleted, nonanemic women

Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial

Iron supplementation for unexplained fatigue in non-anaemic women: double blind randomised placebo controlled trial

Intravenous iron for the treatment of fatigue in nonanemic, premenopausal women with low serum ferritin concentration

Four weeks of IV iron supplementation reduces perceived fatigue and mood disturbance in distance runners

A Blinded, Randomized, Placebo-Controlled Study to Investigate the Efficacy and Safety of Ferric Carboxymaltose in Iron-Deficient Patients with Fibromyalgia

Effects of iron supplementation versus dietary iron on the nutritional iron status: Systematic review with meta-analysis of randomized controlled trials.

Comparative efficacy of intravenous and oral iron supplements for the treatment of iron deficiency in patients with heart failure: A network meta-analysis of randomized controlled trials.

Iron is one of the most abundant minerals on Earth. It occurs naturally in various foods such as oysters, legumes, <a href="/foods/chocolate/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Chocolate&lt;/h6&gt;&lt;p&gt;Chocolate is made from roasted and ground cacao seeds (aka beans) and has been consumed by cultures around the world for centuries. Cacao is thought to have health benefits due to its high content of polyphenols and flavonoids.&lt;/p&gt;&lt;/div&gt;">chocolate</a>, spinach, beef, and <a href="/foods/potatoes/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Potatoes&lt;/h6&gt;&lt;p&gt;Potatoes are starchy tubers that contain a modest amount of complete protein and a broad array of vitamins and minerals. When eaten boiled or baked without calorie-dense toppings, they are among the most filling foods per calorie, but when fried they are less filling and are associated with an elevated risk of weight gain, type 2 diabetes, and cardiovascular disease in observational studies.&lt;/p&gt;&lt;/div&gt;">potatoes</a>, and is added to some foods (e.g., cereals) as a fortification measure. Iron is also sold as a supplement in the form of capsules, tablets, or liquid. In hospital settings, it can be administered through intravenous (IV) or intramuscular (IM) injection.[reference|url=https://ods.od.nih.gov/factsheets/iron-HealthProfessional/|title=Iron Fact Sheet for Health Professionals. MedlinePlus. National Institutes of Health (NIH) Office of Dietary Supplements (ODS). Updated 2023 Jun 15; cited 2023 December 5]
Dietary iron comes in two primary forms: heme iron and non-heme iron. Heme iron is more readily absorbed; it is formed when iron binds to a heterocyclic organic compound called porphyrin. Heme iron is a component of hemoproteins like <a href="/outcomes/hemoglobin/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Hemoglobin&lt;/h6&gt;&lt;p&gt;Hemoglobin is the protein that carries oxygen in red blood cells for delivery to tissues throughout the body.&lt;/p&gt;&lt;/div&gt;">hemoglobin</a> (Hb), an oxygen transport protein, and <a href="/outcomes/myoglibin/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Myoglobin&lt;/h6&gt;&lt;p&gt;Myoglobin is like the &quot;muscle version&quot; of hemoglobin: it is an iron- and oxygen-binding protein found in muscles, whose function is to store oxygen (in contrast to hemoglobin, whose function is to transport it). Myoglobin's oxygen affinity is higher than hemoglobin's.&lt;/p&gt;&lt;/div&gt;">myoglobin</a>, an oxygen-storage protein found in muscle tissues. Animal products (e.g., meat, poultry, and fish) contain both heme and non-heme iron, whereas plant-based and iron-fortified foods only provide non-heme iron, which is less easily absorbed by the body.[reference|url=https://ods.od.nih.gov/factsheets/iron-HealthProfessional/|title=Iron Fact Sheet for Health Professionals. MedlinePlus. National Institutes of Health (NIH) Office of Dietary Supplements (ODS). Updated 2023 Jun 15; cited 2023 December 5]
Additionally, iron is a constituent of the iron-sulfur clusters (ISCs)[reference|url=https://pubmed.ncbi.nlm.nih.gov/19021507|title=Iron-sulfur cluster biosynthesis.|published=2008-Dec|authors=Bandyopadhyay S, Chandramouli K, Johnson MK|journal=Biochem Soc Trans|] found in many proteins; iron is also present in proteins responsible for iron storage and transport (i.e., <a href="/outcomes/transferrin/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Transferrin&lt;/h6&gt;&lt;p&gt;Transferrin is a protein found in the blood that plays a role in iron metabolism. Along with other biomarkers, transferrin levels can be used to assess the level of iron in the body.&lt;/p&gt;&lt;/div&gt;">transferrin</a>, <a href="/supplements/lactoferrin/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Lactoferrin&lt;/h6&gt;&lt;p&gt;Lactoferrin is an iron-binding glycoprotein found in the milk of mammals. Colostrum (the first milk after a baby is born) contains especially high levels of lactoferrin. Research suggests that lactoferrin exhibits antimicrobial, antiviral, antifungal, and antiparasitic properties.&lt;/p&gt;&lt;/div&gt;">lactoferrin</a>, <a href="/outcomes/ferritin/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Ferritin&lt;/h6&gt;&lt;p&gt;Ferritin is the primary protein for storing iron in the body. Ferritin levels are generally used as an indirect measure of iron levels (e.g., for diagnosis of anemia). However, in some conditions, ferritin levels can remain high when iron levels are low.&lt;/p&gt;&lt;/div&gt;">ferritin</a>, hemosiderin).[reference|url=https://www.ncbi.nlm.nih.gov/books/NBK222309/|title=Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Chapter 9, Iron|authors=Institute of Medicine (US) Panel on Micronutrients|published=2001]

Although iron is typically prescribed during pregnancy to prevent IDA,[reference|url=https://pubmed.ncbi.nlm.nih.gov/37069552|title=Role of iron in the reduction of anemia among women of reproductive age in low-middle income countries: insights from systematic review and meta-analysis.|published=2023-Apr-17|authors=Ali SA, Razzaq S, Aziz S, Allana A, Ali AA, Naeem S, Khowaja N, Ur Rehman F|journal=BMC Womens Health|][reference|url=https://pubmed.ncbi.nlm.nih.gov/37403900|title=Iron supplements in pregnant women with normal iron status: A systematic review and meta-analysis.|published=2023-Sep|authors=Hansen R, Sejer EPF, Holm C, Schroll JB|journal=Acta Obstet Gynecol Scand|] regardless of the mother’s iron levels, more studies should be conducted to verify its benefits throughout pregnancy and after childbirth.
One meta-analysis has assessed the effect of daily iron supplementation in pregnant iron-replete women and found that it may reduce both maternal IDA and maternal ID at term (i.e., at 37 weeks gestation or later). The results also suggested that daily oral iron supplementation may decrease the risk of newborns being small for gestational age (SGA) (i.e., having a birth weight below the 10th percentile for their gestational age) or low birthweight (LBW) (i.e., having a birth weight lower than 2500 g).[reference|url=https://pubmed.ncbi.nlm.nih.gov/37403900|title=Iron supplements in pregnant women with normal iron status: A systematic review and meta-analysis.|published=2023-Sep|authors=Hansen R, Sejer EPF, Holm C, Schroll JB|journal=Acta Obstet Gynecol Scand|] Another meta-analysis, which included pregnant and non-pregnant women of reproductive age with IDA, found a significant increase in hemoglobin and ferritin levels following iron supplementation.[reference|url=https://pubmed.ncbi.nlm.nih.gov/37069552|title=Role of iron in the reduction of anemia among women of reproductive age in low-middle income countries: insights from systematic review and meta-analysis.|published=2023-Apr-17|authors=Ali SA, Razzaq S, Aziz S, Allana A, Ali AA, Naeem S, Khowaja N, Ur Rehman F|journal=BMC Womens Health|] However, both meta-analyses presented high heterogeneity, risk of bias, and low to moderate levels of evidence, leaving some questions about the benefits and safety of preventative iron supplementation unanswered.

Oral iron replacement therapy is typically the first-line treatment for IDA. Iron is available in different forms (e.g., tablets, liquid) and compounds (e.g., ferrous sulfate, ferrous fumarate, ferrous bisglycinate, etc.), each of which provides different amounts of elemental iron.[reference|url=https://pubmed.ncbi.nlm.nih.gov/37209050|title=Iron Preparations in the Management of Iron Deficiency Anemia in Infants and Children: A Systematic Review and Meta-Analysis.|published=2023-Sep-15|authors=Arulparithi CS, Arunbabu T, Manjani S|journal=Indian Pediatr|]
Here are some of the most common forms of iron found in supplements:
<table class="table table-bordered markdown-table">
<thead>
<tr>
<th>Iron salt form</th>
<th>Elemental iron (%)</th>
<th>Elemental iron (mg)</th>
</tr>
</thead>
<tbody>
<tr>
<td>Ferrous sulfate</td>
<td>20</td>
<td>64</td>
</tr>
<tr>
<td>Ferrous fumarate</td>
<td>33</td>
<td>99</td>
</tr>
<tr>
<td>Ferrous gluconate</td>
<td>12</td>
<td>39</td>
</tr>
</tbody>
</table>
Formulations containing ferrous iron (Fe2+) are more bioavailable, but they are also more likely to cause side effects. In contrast, ferric iron (Fe3+) preparations are usually better-tolerated but not as effective.[reference|url=https://pubmed.ncbi.nlm.nih.gov/37357449|title=Iron Deficiency Anemia in Infancy, Childhood, and Adolescence.|published=2023-Jul|authors=Aksu T, Ünal Ş|journal=Turk Arch Pediatr|]
Ferrous bisglycinate is another popular iron form found in supplements, wherein iron is chelated to two glycine molecules. Ferrous bisglycinate is marketed as more bioavailable than the other iron salts, and as having fewer gastrointestinal side effects. Furthermore, due to its stable chemical structure, ferrous bisglycinate is less affected by common iron absorption inhibitors (e.g., phytates found in cereals). However, although results from a meta-analysis showed that while iron bisglycinate was more effective than other iron salts in increasing hemoglobin levels in pregnant women, in children its effectiveness was comparable to other iron preparations.[reference|url=https://pubmed.ncbi.nlm.nih.gov/36728680|title=The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: a systematic review and meta-analysis of randomized controlled trials.|published=2023-Jul-10|authors=Fischer JAJ, Cherian AM, Bone JN, Karakochuk CD|journal=Nutr Rev|]
Heme iron polypeptide (HIP) is another form of iron. It is commonly produced from swine or bovine blood using enzymatic hydrolysis, in which heme iron is bound to peptides derived from the digested hemoglobin.[reference|url=https://pubmed.ncbi.nlm.nih.gov/37685181|title=Production and Characterization of Heme Iron Polypeptide from the Blood of Skipjack Tuna () Using Enzymatic Hydrolysis for Food Supplement Application.|published=2023-Aug-29|authors=Tansukkasem S, Kaewpathomsri P, Jonjaroen V, Payongsri P, Lertsiri S, Niamsiri N|journal=Foods|] This form of iron has increased in popularity due to claims that it has enhanced bioavailability and fewer gastrointestinal side effects than other iron compounds. One study showed that when compared to ferrous fumarate, HIP taken with meals significantly increased iron absorption, but was not associated with side effects.[reference|url=https://doi.org/10.1016/S0271-5317(00)00215-3|title=Clinical studies of hip: An oral heme-iron product|authors=Seligman et al.|journal=Nutrition Research|published=2000-09-01] However, larger studies should be conducted to compare its efficacy and safety to other iron preparations.
When iron is administered intravenously, IV ferric carboxymaltose and IV iron sucrose appear to be the most effective forms at increasing hemoglobin and ferritin levels within a period of four weeks.[reference|url=https://pubmed.ncbi.nlm.nih.gov/34171281|title=Iron preparations for women of reproductive age with iron deficiency anaemia in pregnancy (FRIDA): a systematic review and network meta-analysis.|published=2021-Jul|authors=Rogozińska E, Daru J, Nicolaides M, Amezcua-Prieto C, Robinson S, Wang R, Godolphin PJ, Saborido CM, Zamora J, Khan KS, Thangaratinam S|journal=Lancet Haematol|]
Finally, one <a href="/glossary/in-vitro-study/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;In Vitro Study&lt;/h6&gt;&lt;p&gt;&lt;em&gt;In vitro&lt;/em&gt; (Latin for “within the glass”) refers to studies that are performed outside of a living organism. In scientific research, this often involves performing experiments on bacterial, animal, or human cells growing in lab culture dishes.&lt;/p&gt;&lt;/div&gt;">in vitro</a> study compared modified-release iron supplements to immediate-release formulations and found that the slow-release tablets did not completely dissolve even after 24 hours, and iron uptake was considerably lower compared to regular tablets.[reference|url=https://pubmed.ncbi.nlm.nih.gov/24482777|title=Comparison study of oral iron preparations using a human intestinal model.|published=2013|authors=Zariwala MG, Somavarapu S, Farnaud S, Renshaw D|journal=Sci Pharm|] Although modified-release iron preparations may be better tolerated, with fewer side effects, they may not be as effective. These findings need further clarification through in vivo clinical studies.

It remains unclear whether iron supplementation is beneficial for athletes with ID but not anemia, or for those with normal iron status. While there is some evidence that iron supplementation may improve fatigue in iron-deficient athletes and non-athletes,[reference|url=https://pubmed.ncbi.nlm.nih.gov/29626044|title=Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials|published=2018 Apr 5|authors=Houston BL, Hurrie D, Graham J, Perija B, Rimmer E, Rabbani R, Bernstein CN, Turgeon AF, Fergusson DA, Houston DS, Abou-Setta AM, Zarychanski R|journal=BMJ Open|] and intensive training is a potential cause of iron depletion,[reference|url=https://pubmed.ncbi.nlm.nih.gov/25918331|title=Exercise-induced anaemia: a forgotten cause of iron deficiency anaemia in young adults.|published=2015-May|authors=Wouthuyzen-Bakker M, van Assen S|journal=Br J Gen Pract|] only a few studies have investigated the benefits of iron supplementation in athletes with adequate iron levels to replenish iron loss due to training.
In one study involving iron-sufficient soccer players during training, iron supplementation was found to maintain ferritin and iron store levels, and these levels decreased once the supplementation was interrupted.[reference|url=https://pubmed.ncbi.nlm.nih.gov/9284502|title=Iron stores in professional athletes throughout the sports season.|published=1997-Oct|authors=Escanero JF, Villanueva J, Rojo A, Herrera A, del Diego C, Guerra M|journal=Physiol Behav|] However, this study did not observe any significant difference in transferrin levels, which provide information on the iron levels required for erythropoiesis (red blood cell production), and it lacked a control group.
In another study, swimmers between the ages of 12 and 17 were either given an iron supplement (47 mg iron daily) or instructed to consume an iron-rich diet. Both interventions failed to significantly alter either the participants’ iron status (measured as iron, ferritin, and transferrin levels) or their athletic performance.[reference|url=https://pubmed.ncbi.nlm.nih.gov/15162251|title=Effects of iron intake through food or supplement on iron status and performance of healthy adolescent swimmers during a training season.|published=2004-May|authors=Tsalis G, Nikolaidis MG, Mougios V|journal=Int J Sports Med|]

While most people obtain adequate iron from their diet, there are situations where iron supplementation may be required.[reference|url=https://ods.od.nih.gov/factsheets/iron-HealthProfessional/|title=Iron Fact Sheet for Health Professionals. MedlinePlus. National Institutes of Health (NIH) Office of Dietary Supplements (ODS). Updated 2023 Jun 15; cited 2023 December 5] For instance, the World Health Organization (WHO) recommends daily oral iron supplementation for all children living in areas where anemia prevalence exceeds 40%.
Frequent blood donation can also deplete iron levels, potentially leading to anemia, and therefore supplementation may be necessary, especially for people at high risk of deficiency, such as women.[reference|url=https://pubmed.ncbi.nlm.nih.gov/1889481|title=Influence of blood donation on iron stores assessed by serum ferritin and haemoglobin in a population survey of 1433 Danish males.|published=1991-Aug|authors=Milman N, Kirchhoff M|journal=Eur J Haematol|][reference|url=https://pubmed.ncbi.nlm.nih.gov/1926310|title=A prospective study of blood donations in healthy elderly persons|published=1991 Oct|authors=Garry PJ, VanderJagt DJ, Wayne SJ, Koehler KH, Rhyne RL, Simon TL|journal=Transfusion|] However, evidence that iron supplementation is effective in preserving iron levels is still weak.
Finally, individuals following a vegetarian or <a href="/diets/vegan/" class="popover" data-tooltip='&lt;div&gt;&lt;h6&gt;Vegan Diet&lt;/h6&gt;&lt;p&gt;Vegan diets exclude all animal products. Veganism has rapidly increased in popularity, although randomized trials are still few in number. Trials do show promise for a variety of outcomes, from weight loss to autoimmunity, although comparisons to other popular diets are rare. A vegan diet should be balanced and low in processed foods (e.g. a "Whole Food Plant-Based diet") for optimal results.&lt;/p&gt;&lt;/div&gt;'>vegan diet</a> may need to increase their iron intake,[reference|url=https://ods.od.nih.gov/factsheets/iron-HealthProfessional/|title=Iron Fact Sheet for Health Professionals. MedlinePlus. National Institutes of Health (NIH) Office of Dietary Supplements (ODS). Updated 2023 Jun 15; cited 2023 December 5] mainly because plant-based foods contain non-heme iron, which is not as bioavailable as the heme iron found in meat.

Iron plays a pivotal role in numerous biological functions and is often the first-line treatment for <a href="/conditions/iron-deficiency-anemia/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Iron Deficiency Anemia&lt;/h6&gt;&lt;p&gt;Iron deficiency anemia occurs when the body does not have enough iron to produce healthy red blood cells to transport oxygen in the blood. Iron deficiency anemia can be caused by excessive blood loss or reduced iron absorption or intake. It can be treated with oral iron supplementation, though there is a wide range of individual tolerance for, and effectiveness of, iron supplements.&lt;/p&gt;&lt;/div&gt;">iron deficiency anemia</a> (IDA). While specific guidelines exist for treating IDA with iron, there is still insufficient evidence to prove the benefits of iron supplementation in individuals with iron deficiency (ID) who are not anemic.[reference|url=https://pubmed.ncbi.nlm.nih.gov/29626044|title=Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials|published=2018 Apr 5|authors=Houston BL, Hurrie D, Graham J, Perija B, Rimmer E, Rabbani R, Bernstein CN, Turgeon AF, Fergusson DA, Houston DS, Abou-Setta AM, Zarychanski R|journal=BMJ Open|]
In clinical practice, iron is commonly prescribed to menstruating women due to the increased blood loss, and during pregnancy to meet heightened metabolic demands and prevent IDA, which could have serious consequences for both the mother and the baby.[reference|url=https://pubmed.ncbi.nlm.nih.gov/37069552|title=Role of iron in the reduction of anemia among women of reproductive age in low-middle income countries: insights from systematic review and meta-analysis.|published=2023-Apr-17|authors=Ali SA, Razzaq S, Aziz S, Allana A, Ali AA, Naeem S, Khowaja N, Ur Rehman F|journal=BMC Womens Health|][reference|url=https://pubmed.ncbi.nlm.nih.gov/37403900|title=Iron supplements in pregnant women with normal iron status: A systematic review and meta-analysis.|published=2023-Sep|authors=Hansen R, Sejer EPF, Holm C, Schroll JB|journal=Acta Obstet Gynecol Scand|] 
ID is also a risk factor for <a href="/conditions/heart-failure/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Heart Failure&lt;/h6&gt;&lt;p&gt;&lt;em&gt;Heart failure&lt;/em&gt; (HF), also known as &lt;em&gt;congestive heart failure&lt;/em&gt;, is a progressive condition that occurs when the heart cannot pump enough blood to oxygenate the tissues in the brain and body. It is typically caused by other heart conditions that change the heart's structure and function. Heart failure is common, and is the leading cause of hospitalization for patients over age 65 in the U.S.&lt;/p&gt;&lt;/div&gt;">heart failure</a> (HF). Iron supplementation in individuals affected by HF appears to reduce the rates of hospitalization and the severity of HF symptoms.[reference|url=https://pubmed.ncbi.nlm.nih.gov/37383191|title=Intravenous iron therapy among patients with heart failure and iron deficiency: An updated meta-analysis of randomized controlled trials.|published=2023-Jun|authors=Hamed M, Elseidy SA, Ahmed A, Thakker R, Mansoor H, Khalili H, Mohsen A, Mamas MA, Banerjee S, Kumbhani DJ, Elgendy IY, Elbadawi A|journal=Heliyon|][reference|url=https://pubmed.ncbi.nlm.nih.gov/37429060|title=Meta-Analysis of Efficacy and Safety of Intravenous Iron in Patients With Iron Deficiency and Heart Failure With Reduced Ejection Fraction.|published=2023-Sep-01|authors=Hamza M, Sattar Y, Manasrah N, Patel NN, Rashdi A, Khanal R, Naveed H, Zafar M, Khan AM, Alharbi A, Aamir M, Gonuguntla K, Raina S, Balla S|journal=Am J Cardiol|] Hemoglobin, ferritin and <a href="/outcomes/left-ventricular-ejection-fraction/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Left Ventricular Ejection Fraction&lt;/h6&gt;&lt;p&gt;Left ventricular ejection fraction (LVEF) is the capacity of the heart to 'pulse' blood out of cardiac tissue and into circulation, and is a biomarker of cardiac health. The reduction in LVEF seen during cardiac ailments tends to be a focus of rehabilitation.&lt;/p&gt;&lt;/div&gt;">left ventricular ejection fraction</a> (LVEF) levels also seem to be increased by iron,[reference|url=https://pubmed.ncbi.nlm.nih.gov/37383191|title=Intravenous iron therapy among patients with heart failure and iron deficiency: An updated meta-analysis of randomized controlled trials.|published=2023-Jun|authors=Hamed M, Elseidy SA, Ahmed A, Thakker R, Mansoor H, Khalili H, Mohsen A, Mamas MA, Banerjee S, Kumbhani DJ, Elgendy IY, Elbadawi A|journal=Heliyon|] and one meta-analysis also noted that exercise capacity and quality of life were improved after iron supplementation in people with HF.[reference|url=https://pubmed.ncbi.nlm.nih.gov/37429060|title=Meta-Analysis of Efficacy and Safety of Intravenous Iron in Patients With Iron Deficiency and Heart Failure With Reduced Ejection Fraction.|published=2023-Sep-01|authors=Hamza M, Sattar Y, Manasrah N, Patel NN, Rashdi A, Khanal R, Naveed H, Zafar M, Khan AM, Alharbi A, Aamir M, Gonuguntla K, Raina S, Balla S|journal=Am J Cardiol|]
Iron is also a key component in the brain, and studies involving children have shown that supplementation may improve memory and concentration.[reference|url=https://pubmed.ncbi.nlm.nih.gov/37368919|title=Effects of iron supplementation on cognitive development in school-age children: Systematic review and meta-analysis.|published=2023|authors=Gutema BT, Sorrie MB, Megersa ND, Yesera GE, Yeshitila YG, Pauwels NS, De Henauw S, Abbeddou S|journal=PLoS One|] However, more quality research is needed to verify these results.
The question of whether iron supplementation benefits infants and young adults remains a topic of debate necessitating further research. One meta-analysis, which included children and adolescents ranging from 1 month to 19 years old, found that iron supplementation increased Hb and ferritin levels, particularly with frequent supplementation over longer periods, and resulted in reduced prevalence of overall anemia, ID, and IDA.[reference|url=https://pubmed.ncbi.nlm.nih.gov/36849195|title=Oral iron supplementation and anaemia in children according to schedule, duration, dose and cosupplementation: a systematic review and meta-analysis of 129 randomised trials.|published=2023-Feb|authors=Andersen CT, Marsden DM, Duggan CP, Liu E, Mozaffarian D, Fawzi WW|journal=BMJ Glob Health|]
Finally, one meta-analysis demonstrated that both oral and IV iron supplementation appeared to improve symptoms of <a href="/conditions/restless-leg-syndrome/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Restless Leg Syndrome&lt;/h6&gt;&lt;p&gt;Restless leg syndrome (RLS) is characterized by uncomfortable sensations in the legs that are momentarily relieved upon movement. The sensations typically worsen at night when the legs are at rest, which is incredibly disruptive to sleep quality.&lt;/p&gt;&lt;/div&gt;">restless leg syndrome</a> (RLS). Specifically, IV supplementation with ferric carboxymaltose (FCM) was associated with a significant improvement in <a href="/outcomes/quality-of-life/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Quality of Life&lt;/h6&gt;&lt;p&gt;Quality of life (QOL) refers to a general, all concompassing, response as to how tolerance and enjoyable one's living conditions are. QOL is impaired in various disease states that reduce functionality or cause pain, and treating these symptoms causes an increase in QOL.&lt;/p&gt;&lt;/div&gt;">quality of life</a> (QOL) scores, although it had no noticeable effect on sleep quality.[reference|url=https://pubmed.ncbi.nlm.nih.gov/30798983|title=Iron supplementation for restless legs syndrome - A systematic review and meta-analysis|published=2019 May|authors=Tomer Avni, Shelley Reich, Nirit Lev, Anat Gafter-Gvili|journal=Eur J Intern Med|]

Iron supplements should be used cautiously, only when required, and in accordance with recommended doses. Prolonged use of iron supplements or an excess of iron in the system can lead to adverse side effects.
Iron supplements frequently result in gastrointestinal discomfort, including symptoms such as <a href="/outcomes/nausea-symptoms/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Nausea Symptoms&lt;/h6&gt;&lt;p&gt;Nausea is the feeling of acute sickness that may result in vomiting and loss of appetite. Some supplements are known as antiemetics, and are used to reduce the sensation of nausea when taken.&lt;/p&gt;&lt;/div&gt;">nausea</a>, <a href="/outcomes/abdominal-pain/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Abdominal Pain&lt;/h6&gt;&lt;p&gt;Abdominal pain is a pain that originates within the abdomen. It can occur due to a variety of factors that may be benign such as indigestion or more serious conditions such as colon cancer.&lt;/p&gt;&lt;/div&gt;">abdominal pain</a>, dark stool, <a href="/outcomes/heartburn-symptoms/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Heartburn Symptoms&lt;/h6&gt;&lt;p&gt;Heartburn is a painful sensation felt in the chest due to stomach acid traveling up into the esophagus. Symptoms are usually worse after eating, lying down, or bending over.&lt;/p&gt;&lt;/div&gt;">heartburn</a>, and <a href="/conditions/constipation/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Constipation&lt;/h6&gt;&lt;p&gt;Constipation occurs when the process of defecation is impaired to such a degree that a person can no longer easily pass stool.&lt;/p&gt;&lt;/div&gt;">constipation</a>, and other side effects such as <a href="/outcomes/headaches/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Headaches&lt;/h6&gt;&lt;p&gt;Headaches are characterized by pain throughout the head and/or face. The location, intensity, and causes of headaches can vary.&lt;/p&gt;&lt;/div&gt;">headache</a>. This can be a significant challenge for individuals with IDA, who may find it difficult to adhere to their treatment recommendations.[reference|url=https://pubmed.ncbi.nlm.nih.gov/37368919|title=Effects of iron supplementation on cognitive development in school-age children: Systematic review and meta-analysis.|published=2023|authors=Gutema BT, Sorrie MB, Megersa ND, Yesera GE, Yeshitila YG, Pauwels NS, De Henauw S, Abbeddou S|journal=PLoS One|]
Although ferritin, hemosiderin, and transferrin play essential roles in regulating iron levels in the system, an excessive amount of free iron can trigger the production of free radicals and increase oxidative stress. This can potentially lead to damage to proteins and cells, and harm the body.[reference|url=https://www.intechopen.com/chapters/44692|title=Iron Supplementation and Physical Performance|published=2013 May|authors=Deli C. K., et al|journal=Current Issues in Sports and Exercise Medicine][reference|url=https://pubmed.ncbi.nlm.nih.gov/21855608|title=Non-transferrin bound iron: a key role in iron overload and iron toxicity|published=2012 Mar|authors=Brissot P, Ropert M, Le Lan C, Loréal O|journal=Biochim Biophys Acta|] Diseases characterized by iron overload include hemochromatosis, a hereditary disease in which iron builds up to toxic levels in the body, which can lead to damage to organs such as liver, joints pancreas or heart.[reference|url=https://pubmed.ncbi.nlm.nih.gov/37299408|title=Nutritional Aspects of Iron in Health and Disease.|published=2023-May-24|authors=Charlebois E, Pantopoulos K|journal=Nutrients|]
Additionally, multiple observational studies have reported that regular consumption of dietary iron, especially heme iron sourced from meat products, may predispose one to numerous diseases (e.g., <a href="/conditions/type-2-diabetes/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Type 2 Diabetes&lt;/h6&gt;&lt;p&gt;Type 2 diabetes (T2D) is a disease in which blood glucose levels are too high. It is characterized by insulin resistance in muscle, fat, and pancreas cells and an inability of the pancreas to manufacture enough insulin to control blood glucose levels. T2D is strongly associated with excess body fat, and weight loss induced by lifestyle changes is extremely effective for treating T2D.&lt;/p&gt;&lt;/div&gt;">type 2 diabetes</a>, <a href="/conditions/cardiovascular-disease/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Cardiovascular Disease&lt;/h6&gt;&lt;p&gt;Cardiovascular disease (CVD) is a broad term that refers to various diseases of the heart and blood vessels. Atherosclerotic CVD (ASCVD) is the most common subtype of CVD and causes strokes and heart attacks.&lt;/p&gt;&lt;/div&gt;">cardiovascular disease</a>, coronary heart disease) and may increase the risk of some cancers (e.g., <a href="/conditions/breast-cancer/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Breast Cancer&lt;/h6&gt;&lt;p&gt;Breast cancer is the second most common cancer in women, after skin cancer. It affects men very rarely. It is most treatable when caught early, therefore it is important to do regular breast exams and regular physician visits.&lt;/p&gt;&lt;/div&gt;">breast</a>, <a href="/conditions/colorectal-cancer/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Colorectal Cancer&lt;/h6&gt;&lt;p&gt;&lt;em&gt;Colorectal cancer&lt;/em&gt; (CRC) occurs when tumors form in the lining of the colon or rectum (which together make up the large intestine). Symptoms include a change in bowel habits, fatigue, and unexplained weight loss. CRC is diagnosed after a physical exam of the colon and rectum. It can be treated in a variety of ways, including surgery, immunotherapy, and chemotherapy.&lt;/p&gt;&lt;/div&gt;">colorectal</a>, and <a href="/conditions/esophageal-cancer/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Esophageal Cancer&lt;/h6&gt;&lt;p&gt;Esophageal cancer is characterized by abnormal cell growth and replication in the esophagus, a hollow, muscular tube that connects the throat to the stomach.&lt;/p&gt;&lt;/div&gt;">esophageal cancer</a>). However, the majority of these claims are based on self-reported food diaries or food questionnaires, and the level of evidence is weak. Furthermore, it’s important to highlight that processed meat does not only contain heme iron, but other potentially harmful substances (e.g., nitrite, nitrate, heterocyclic amines) which may be confounding factors that also raise the risk of some diseases.[reference|url=https://pubmed.ncbi.nlm.nih.gov/37299408|title=Nutritional Aspects of Iron in Health and Disease.|published=2023-May-24|authors=Charlebois E, Pantopoulos K|journal=Nutrients|]
In children, low doses of iron may cause diarrhea, but they do not appear to increase the risk of infections at the recommended dosage. Nevertheless, the World Health Organization (WHO) advises monitoring children in countries at high risk of malaria when receiving iron supplementation, as it may both increase the risk of contracting the disease and potentially worsen its effects. The mechanism by which iron interacts with malaria is still not fully understood.[reference|url=https://pubmed.ncbi.nlm.nih.gov/37368919|title=Effects of iron supplementation on cognitive development in school-age children: Systematic review and meta-analysis.|published=2023|authors=Gutema BT, Sorrie MB, Megersa ND, Yesera GE, Yeshitila YG, Pauwels NS, De Henauw S, Abbeddou S|journal=PLoS One|][reference|url=https://pubmed.ncbi.nlm.nih.gov/30699468|title=Intermittent iron supplementation for reducing anaemia and its associated impairments in adolescent and adult menstruating women|published=2019 Jan 31|authors=Fernández-Gaxiola AC, De-Regil LM|journal=Cochrane Database Syst Rev|]

Heme iron is more readily absorbed compared to non-heme iron, but the bioavailability of iron in the body can be influenced by several foods and dietary components. In individuals following a mixed diet, which includes fruit, vegetables, meat, and seafood, the bioavailability of iron ranges from approximately 14% to 18%. For vegetarian diets, iron bioavailability can range from 5% to 12%.[reference|url=https://ods.od.nih.gov/factsheets/iron-HealthProfessional/|title=Iron Fact Sheet for Health Professionals. MedlinePlus. National Institutes of Health (NIH) Office of Dietary Supplements (ODS). Updated 2023 Jun 15; cited 2023 December 5]
Animal protein appears to increase non-heme iron absorption from non-meat produce (e.g., vegetables, grains) when these foods are consumed in the same meal. However, this effect was less pronounced for wheat than for other plant-based foods.[reference|url=https://pubmed.ncbi.nlm.nih.gov/2658489|title=The effect of dietary proteins on iron bioavailability in man|published=1989|authors=Lynch SR, Hurrell RF, Dassenko SA, Cook JD|journal=Adv Exp Med Biol|][reference|url=https://pubmed.ncbi.nlm.nih.gov/16484527|title=Meat consumption in a varied diet marginally influences nonheme iron absorption in normal individuals|published=2006 Mar|authors=Reddy MB, Hurrell RF, Cook JD|journal=J Nutr|] Additionally, studies have yielded mixed results regarding the combination of pork meat with meals high in phytates (which can be found in certain legumes and vegetables), indicating that phytate may counteract the positive effects of animal protein on non-heme iron absorption.[reference|url=https://pubmed.ncbi.nlm.nih.gov/16115336|title=Pork meat increases iron absorption from a 5-day fully controlled diet when compared to a vegetarian diet with similar vitamin C and phytic acid content|published=2005 Jul|authors=Bach Kristensen M, Hels O, Morberg C, Marving J, Bügel S, Tetens I|journal=Br J Nutr|][reference|url=https://pubmed.ncbi.nlm.nih.gov/12499338|title=Nonheme-iron absorption from a phytate-rich meal is increased by the addition of small amounts of pork meat|published=2003 Jan|authors=Baech SB, Hansen M, Bukhave K, Jensen M, Sørensen SS, Kristensen L, Purslow PP, Skibsted LH, Sandström B|journal=Am J Clin Nutr|]
It’s often recommended that iron be taken with <a href="/supplements/vitamin-c/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Vitamin C&lt;/h6&gt;&lt;p&gt;Vitamin C, or ascorbic acid, is an essential vitamin and a very popular supplement due to its antioxidant properties, safety profile, and low price. Many people supplement with vitamin C because it is believed to reduce symptoms of the common cold.&lt;/p&gt;&lt;/div&gt;">Vitamin C</a> (ascorbic acid) supplements or vitamin C-rich foods. Theoretically, ascorbic acid can facilitate the reduction of ferric iron to its more bioavailable form (ferrous iron), and can chelate iron ions (i.e., bond with them) to enhance their solubility and absorption from the intestines into the bloodstream.[reference|url=https://pubmed.ncbi.nlm.nih.gov/37739692|title=Treatment efficacy of vitamin C or ascorbate given as co-intervention with iron for anemia - A systematic review and meta-analysis of experimental studies.|published=2023-Oct|authors=Loganathan V, Bharathi A, Prince AM, Ramakrishnan J|journal=Clin Nutr ESPEN|] Furthermore, ascorbate (a mineral salt of ascorbic acid) regulates the uptake of iron by transferrin, which is why scurvy (a disease resulting from a vitamin C deficiency) is often associated with some degree of iron-deficiency anemia.[reference|url=https://pubmed.ncbi.nlm.nih.gov/25048971|title=The active role of vitamin C in mammalian iron metabolism: much more than just enhanced iron absorption!|published=2014-Oct|authors=Lane DJ, Richardson DR|journal=Free Radic Biol Med|] However, two meta-analyses both found no difference in hemoglobin and ferritin levels when iron was supplemented with vitamin C, compared to iron alone,[reference|url=https://pubmed.ncbi.nlm.nih.gov/37739692|title=Treatment efficacy of vitamin C or ascorbate given as co-intervention with iron for anemia - A systematic review and meta-analysis of experimental studies.|published=2023-Oct|authors=Loganathan V, Bharathi A, Prince AM, Ramakrishnan J|journal=Clin Nutr ESPEN|][reference|url=https://pubmed.ncbi.nlm.nih.gov/34784635|title=Oral Iron Supplementation in Pregnancy: Current Recommendations and Evidence-Based Medicine.|published=2021-Oct|authors=Duarte AFM, Carneiro ACSV, Peixoto ATBMM, Montenegro DFP, Campos DSC, Alves APR, Costa ARMM, Fino APM|journal=Rev Bras Ginecol Obstet|] suggesting that there is still limited clinical data on the benefits of combining iron and vitamin C.

Iron absorption can be reduced by other vitamins and minerals found both in supplements and foods.
Multiple studies have found that <a href="/supplements/calcium/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Calcium&lt;/h6&gt;&lt;p&gt;Calcium is a dietary macromineral found in high amounts in dairy products, and to a lesser extent in vegetables. Used primarily to support bone health, calcium also has a role in maternal and cardiovascular health.&lt;/p&gt;&lt;/div&gt;">calcium</a> is a strong inhibitor of iron absorption, and avoiding the simultaneous use of calcium and iron supplements may be beneficial. In one study, calcium phosphate inhibited iron absorption from a ferrous sulfate supplement, whether taken with or without food. In contrast, calcium carbonate only inhibited iron absorption when both supplements were consumed with food, suggesting that if a combined iron and calcium carbonate supplement is required, it should be taken between meals.[reference|url=https://pubmed.ncbi.nlm.nih.gov/1984334|title=Calcium supplementation: effect on iron absorption|published=1991 Jan|authors=Cook JD, Dassenko SA, Whittaker P|journal=Am J Clin Nutr|] Calcium citrate, on the other hand, reduced iron absorption both with and without food, but not to a statistically significant degree in one study[reference|url=https://pubmed.ncbi.nlm.nih.gov/1984334|title=Calcium supplementation: effect on iron absorption|published=1991 Jan|authors=Cook JD, Dassenko SA, Whittaker P|journal=Am J Clin Nutr|], and reduced absorption of non-heme iron without food in another study.[reference|url=https://pubmed.ncbi.nlm.nih.gov/29895376|title=Effect of various calcium salts on non-heme iron bioavailability in fasted women of childbearing age|published=2018 Sep|authors=Candia V, Ríos-Castillo I, Carrera-Gil F, Vizcarra B, Olivares M, Chaniotakis S, Pizarro F|journal=J Trace Elem Med Biol|]. The impact of calcium chloride on iron absorption seems to vary depending on whether it’s taken with food[reference|url=https://pubmed.ncbi.nlm.nih.gov/1984335|title=Calcium: effect of different amounts on nonheme- and heme-iron absorption in humans|published=1991 Jan|authors=Hallberg L, Brune M, Erlandsson M, Sandberg AS, Rossander-Hultén L|journal=Am J Clin Nutr|] or without food.[reference|url=https://pubmed.ncbi.nlm.nih.gov/21795430|title=Calcium does not inhibit the absorption of 5 milligrams of nonheme or heme iron at doses less than 800 milligrams in nonpregnant women|published=2011 Sep|authors=Gaitán D, Flores S, Saavedra P, Miranda C, Olivares M, Arredondo M, López de Romaña D, Lönnerdal B, Pizarro F|journal=J Nutr|]
Furthermore, a wide variety of beverages with a high antioxidant content, including coffee and tea, have some acute inhibitory effects on non-heme iron absorption. <a href="/foods/coffee/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Coffee&lt;/h6&gt;&lt;p&gt;Sometimes referred to as liquid gold, coffee is the most popular source of caffeine in North America (and behind only teas worldwide). Also a source of tons of nutrients, and most recently touted as a source of chlorogenic acid and ferulic acid.&lt;/p&gt;&lt;/div&gt;">Coffee</a> may reduce iron absorption,[reference|url=https://pubmed.ncbi.nlm.nih.gov/10999016|title=Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages|published=1999 Apr|authors=R F Hurrell, M Reddy, J D Cook|journal=Br J Nutr|] possibly due to the presence of <a href="/supplements/chlorogenic-acid/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Chlorogenic Acid&lt;/h6&gt;&lt;p&gt;Chlorogenic acid is found in coffee mostly and a lot of plant compounds; it holds promise in many aspects of health and cognition similar to bioflavonoids and shares some effects similar to caffeine but less potent. May decrease the absorption of dietary carbohydrate.&lt;/p&gt;&lt;/div&gt;">chlorogenic acid</a>, a known iron chelator.[reference|url=https://pubmed.ncbi.nlm.nih.gov/9501514|title=Iron chelation by chlorogenic acid as a natural antioxidant.|published=1998-Jan|authors=Kono Y, Kashine S, Yoneyama T, Sakamoto Y, Matsui Y, Shibata H|journal=Biosci Biotechnol Biochem|] This mechanism can be extended to green coffee extract, which is an even richer source of chlorogenic acid. Tea, whether <a href="/foods/green-tea/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Green Tea&lt;/h6&gt;&lt;p&gt;Green tea contains more antioxidants and polyphenols than any other tea variety. It is a major source of the compound &lt;em&gt;epigallocatechin gallate&lt;/em&gt; (EGCG). Green tea is widely used in traditional Chinese medicine and has been linked to a reduced risk for several major diseases. &lt;em&gt;Green Tea Extract&lt;/em&gt; is a common supplement.&lt;/p&gt;&lt;/div&gt;">green</a>[reference|url=https://pubmed.ncbi.nlm.nih.gov/11237939|title=Green tea or rosemary extract added to foods reduces nonheme-iron absorption.|published=2001-Mar|authors=Samman S, Sandström B, Toft MB, Bukhave K, Jensen M, Sørensen SS, Hansen M|journal=Am J Clin Nutr|] or black,[reference|url=https://pubmed.ncbi.nlm.nih.gov/10999016|title=Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages|published=1999 Apr|authors=R F Hurrell, M Reddy, J D Cook|journal=Br J Nutr|] might inhibit iron absorption, possibly due to the presence of catechins[reference|url=https://pubmed.ncbi.nlm.nih.gov/11237939|title=Green tea or rosemary extract added to foods reduces nonheme-iron absorption.|published=2001-Mar|authors=Samman S, Sandström B, Toft MB, Bukhave K, Jensen M, Sørensen SS, Hansen M|journal=Am J Clin Nutr|] and <a href="/supplements/theaflavins/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Theaflavins&lt;/h6&gt;&lt;p&gt;Theaflavins are a group of molecules that are found in black tea (due to an additional fermentation process from green tea) that are said to be the bioactives of black tea.&lt;/p&gt;&lt;/div&gt;">theaflavins</a>.[reference|url=https://pubmed.ncbi.nlm.nih.gov/15041246|title=Reaction of iron(III) with theaflavin: complexation and oxidative products.|published=2004-Apr|authors=O'Coinceanainn M, Bonnely S, Baderschneider B, Hynes MJ|journal=J Inorg Biochem|]
Infusions of <a href="/foods/chamomile/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Chamomile&lt;/h6&gt;&lt;p&gt;Chamomile is commonly consumed as an herbal tea or used as an essential oil in aromatherapy. Due to the high amounts of terpenes and flavonoids in chamomile, it has been used to treat anxiety, gastrointestinal disorders, inflammation, and insomnia.&lt;/p&gt;&lt;/div&gt;">chamomile</a>, lime flower, pennyroyal, peppermint, and vervain may also reduce non-heme iron absorption.[reference|url=https://pubmed.ncbi.nlm.nih.gov/10999016|title=Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages|published=1999 Apr|authors=R F Hurrell, M Reddy, J D Cook|journal=Br J Nutr|]
Rosemary (a source of rosmarinic acid), rich in phytic and phenolic acid, has also been shown to reduce non-heme iron absorption.[reference|url=https://pubmed.ncbi.nlm.nih.gov/11237939|title=Green tea or rosemary extract added to foods reduces nonheme-iron absorption.|published=2001-Mar|authors=Samman S, Sandström B, Toft MB, Bukhave K, Jensen M, Sørensen SS, Hansen M|journal=Am J Clin Nutr|]
Additionally, in one randomized controlled trial, people with beta-thalassemia who took 500 mg of <a href="/supplements/quercetin/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Quercetin&lt;/h6&gt;&lt;p&gt;Quercetin is the most well researched of all bioflavonoids. It is not actually that good of a supplement on its own, but is an interesting research topic. Tons of interactions, and synergistic with other bioflavonoids and increases absorption of Resveratrol and Green Tea Catechins.&lt;/p&gt;&lt;/div&gt;">quercetin</a> (a chelator of iron[reference|url=https://pubmed.ncbi.nlm.nih.gov/16910729|title=Iron chelation by the powerful antioxidant flavonoid quercetin|published=2006 Aug 23|authors=Leopoldini M, Russo N, Chiodo S, Toscano M|journal=J Agric Food Chem|]) per day for 12 weeks alleviated iron overload (a common complication of beta-thalassemia), notably reducing serum iron, ferritin, and inflammatory markers.[reference|url=https://pubmed.ncbi.nlm.nih.gov/31519283|title=The effect of quercetin on iron overload and inflammation in β-thalassemia major patients: A double-blind randomized clinical trial|published=2019 Oct|authors=Sajadi Hezaveh Z, Azarkeivan A, Janani L, Hosseini S, Shidfar F|journal=Complement Ther Med|]
Lastly, although <a href="/supplements/zinc/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Zinc&lt;/h6&gt;&lt;p&gt;Zinc is an essential mineral that is critical for the function of hundreds of enzymes. Consequently, it plays many roles, including in antioxidant enzymes, brain function, and the immune system. Zinc is most commonly taken to reduce the duration of respiratory infections and the common cold.&lt;/p&gt;&lt;/div&gt;">zinc</a> has the potential to reduce the absorption of iron, the effect is inconsistent, and the strength of this effect is unclear, with different studies reporting varying results.[reference|url=https://pubmed.ncbi.nlm.nih.gov/36849195|title=Oral iron supplementation and anaemia in children according to schedule, duration, dose and cosupplementation: a systematic review and meta-analysis of 129 randomised trials.|published=2023-Feb|authors=Andersen CT, Marsden DM, Duggan CP, Liu E, Mozaffarian D, Fawzi WW|journal=BMJ Glob Health|][reference|url=https://pubmed.ncbi.nlm.nih.gov/22297381|title=Acute inhibition of iron bioavailability by zinc: studies in humans|published=2012 Aug|authors=Olivares M, Pizarro F, Ruz M, de Romaña DL|journal=Biometals|][reference|url=https://pubmed.ncbi.nlm.nih.gov/10075338|title=Influence of prenatal iron and zinc supplements on supplemental iron absorption, red blood cell iron incorporation, and iron status in pregnant Peruvian women|published=1999 Mar|authors=O'Brien KO, Zavaleta N, Caulfield LE, Yang DX, Abrams SA|journal=Am J Clin Nutr|][reference|url=https://pubmed.ncbi.nlm.nih.gov/22720141|title=Effect of zinc on efficacy of iron supplementation in improving iron and zinc status in women|published=2012|authors=Nguyen P, Grajeda R, Melgar P, Marcinkevage J, Flores R, Ramakrishnan U, Martorell R|journal=J Nutr Metab|][reference|url=https://pubmed.ncbi.nlm.nih.gov/25192026|title=Oral zinc supplementation decreases the serum iron concentration in healthy schoolchildren: a pilot study|published=2014 Sep 4|authors=de Brito NJ, Rocha ÉD, de Araújo Silva A, Costa JB, França MC, das Graças Almeida M, Brandão-Neto J|journal=Nutrients|] The interaction between zinc and iron seems to be linked to competition for transporters in the liver, such as divalent metal transporter 1 (DMT1), human copper transporter 1 (hCTR1),[reference|url=https://pubmed.ncbi.nlm.nih.gov/22068728|title=Iron, copper, and zinc transport: inhibition of divalent metal transporter 1 (DMT1) and human copper transporter 1 (hCTR1) by shRNA|published=2012 May|authors=Espinoza A, Le Blanc S, Olivares M, Pizarro F, Ruz M, Arredondo M|journal=Biol Trace Elem Res|] and ZRT/IRT-like protein 14 (Zip14).[reference|url=https://pubmed.ncbi.nlm.nih.gov/16950869|title=Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells|published=2006 Sep 12|authors=Liuzzi JP, Aydemir F, Nam H, Knutson MD, Cousins RJ|journal=Proc Natl Acad Sci U S A|] Taking zinc between meals is likely a good way to prevent any interference with iron absorption.
It’s important to note that the typical Western diet is complex and rich in both iron absorption enhancers and inhibitors, whose effects may both be attenuated when these substances are consumed simultaneously.[reference|url=https://ods.od.nih.gov/factsheets/iron-HealthProfessional/|title=Iron Fact Sheet for Health Professionals. MedlinePlus. National Institutes of Health (NIH) Office of Dietary Supplements (ODS). Updated 2023 Jun 15; cited 2023 December 5]

Iron supplementation is often associated with gastrointestinal side effects, which may impact treatment adherence. As a result, researchers have explored different dosages and frequencies of supplementation.
One meta-analysis looked at intermittent (once, twice, or three times per week) iron supplementation vs. daily supplementation for improving iron status and preventing anemia in menstruating adolescent and adult women. Both had similar effects on hemoglobin levels and the risk of anemia. However, daily supplementation proved more effective in increasing ferritin levels (although with low quality of evidence), which may be especially significant in populations with a high prevalence of ID, which is characterized by adequate levels of hemoglobin but low ferritin and/or transferrin saturation.[reference|url=https://doi.org/10.7861/clinmed.2020-0582|title=Iron deficiency without anemia: a diagnosis that matters|journal=Clin Med|authors=Al-Nassem, A. et al|March 2021] Moreover, there were no significant differences in treatment adherence or in the side effects experienced among participants in the two groups.[reference|url=https://pubmed.ncbi.nlm.nih.gov/30699468|title=Intermittent iron supplementation for reducing anaemia and its associated impairments in adolescent and adult menstruating women|published=2019 Jan 31|authors=Fernández-Gaxiola AC, De-Regil LM|journal=Cochrane Database Syst Rev|] There is currently no evidence that intermittent supplementation offers advantages in terms of fewer side effects or improved adherence compared to daily supplementation.
In another study, iron-depleted (but not deficient) participants took the same iron dose either daily or on alternate days for 14 and 28 days, respectively. The alternate-day dosing regimen resulted in reduced levels of hepcidin (a hormone responsible for regulating iron homeostasis in the body) and greater iron absorption. However, the impact on iron status remained unclear because there were no notable differences in serum iron, ferritin, or hemoglobin levels between the two groups at the end of the trial. Additionally, the alternate-day dosing group reported experiencing less nausea but more headaches.[reference|url=https://pubmed.ncbi.nlm.nih.gov/29032957|title=Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials|published=2017 Nov|authors=Stoffel NU, Cercamondi CI, Brittenham G, Zeder C, Geurts-Moespot AJ, Swinkels DW, Moretti D, Zimmermann MB|journal=Lancet Haematol|] A subsequent study by the same author, including individuals with ID, confirmed these findings. However, the study’s duration was too short to assess the long-term effects on iron status.[reference|url=https://pubmed.ncbi.nlm.nih.gov/31413088|title=Iron absorption from supplements is greater with alternate day than with consecutive day dosing in iron-deficient anemic women|published=2019 Aug 14|authors=Stoffel NU, Zeder C, Brittenham GM, Moretti D, Zimmermann MB|journal=Haematologica|]

Understanding the process of iron absorption in the body is key to grasping its mechanism of action. The disparity in absorption between heme and non-heme iron has implications for the amount of elemental iron absorbed in the body, with heme iron, typically found in animal products, being absorbed more efficiently.[reference|url=https://pubmed.ncbi.nlm.nih.gov/1581009|title=Contributions of heme and nonheme iron to human nutrition|published=1992|authors=Carpenter CE, Mahoney AW|journal=Crit Rev Food Sci Nutr|]
Both heme and non-heme iron are primarily absorbed in the duodenum and, to a lesser extent, in the upper jejunum (the first and second sections of the small intestine, respectively). Heme iron enters the gastrointestinal tract as ferrous iron (i.e., with a 2+ oxidation state), which is more easily absorbed, while non-heme iron is typically ingested in its ferric (3+) form. However, for non-heme iron to be absorbed, it must first be reduced into ferrous iron by reductase enzymes (e.g., ascorbate ferrireductase), or other compounds like vitamin C. Ferrous iron is then taken up by enterocytes lining the intestine through the divalent metal transporter 1 (DMT1), and then leaves these cells and enters the bloodstream via ferroportin. Once in the bloodstream, iron is converted back from ferrous to ferric iron and transported by transferrin to various organs and tissues.[reference|url=https://pubmed.ncbi.nlm.nih.gov/17729393|title=Molecular mechanisms involved in intestinal iron absorption|published=2007 Sep 21|authors=Sharp P, Srai SK|journal=World J Gastroenterol|]
After absorption, iron plays a crucial role in several reactions and biological processes within the body, many of which are centered around iron’s roles in protein function and oxygen transport and storage. Iron is required to form hemoglobin (an oxygen-transporter protein) and myoglobin (an oxygen-storage protein). Inadequate iron intake can hinder the production of healthy red blood cells, potentially leading to anemia. In mitochondria, iron serves as a cofactor in proteins that contain iron-sulfur clusters (e.g., flavoproteins), other heme-containing proteins involved in the electron transport chain (e.g., cytochrome c oxidase), and proteins that contain iron ions (e.g., monooxygenases and dioxygenases).[reference|url=https://pubmed.ncbi.nlm.nih.gov/27911100|title=Mitochondria and Iron: current questions.|published=2017-Jan|authors=Paul BT, Manz DH, Torti FM, Torti SV|journal=Expert Rev Hematol|][reference|url=https://pubmed.ncbi.nlm.nih.gov/37383191|title=Intravenous iron therapy among patients with heart failure and iron deficiency: An updated meta-analysis of randomized controlled trials.|published=2023-Jun|authors=Hamed M, Elseidy SA, Ahmed A, Thakker R, Mansoor H, Khalili H, Mohsen A, Mamas MA, Banerjee S, Kumbhani DJ, Elgendy IY, Elbadawi A|journal=Heliyon|] Additionally, iron is involved in cell growth and differentiation, electron transfer reactions for energy production, and the regulation of the expression of some genes.[reference|url=https://www.intechopen.com/chapters/44692|title=Iron Supplementation and Physical Performance|published=2013 May|authors=Deli C. K., et al|journal=Current Issues in Sports and Exercise Medicine]
Iron is also an essential nutrient for brain development and function. It plays a role in energy (ATP) production and neurotransmitter synthesis, as well as in the uptake and degradation of neurotransmitters, all of which are involved in behavior, <a href="/outcomes/memory/" class="popover" data-tooltip="&lt;div&gt;&lt;h6&gt;Memory&lt;/h6&gt;&lt;p&gt;The ability to store and recall information. Memory-boosting supplements have mostly been tested in older people, whose memory has degraded, but this page deals with any form of memory and any study population.&lt;/p&gt;&lt;/div&gt;">memory</a>, learning, and sensory systems.[reference|url=https://pubmed.ncbi.nlm.nih.gov/37368919|title=Effects of iron supplementation on cognitive development in school-age children: Systematic review and meta-analysis.|published=2023|authors=Gutema BT, Sorrie MB, Megersa ND, Yesera GE, Yeshitila YG, Pauwels NS, De Henauw S, Abbeddou S|journal=PLoS One|][reference|url=https://pubmed.ncbi.nlm.nih.gov/36558491|title=Effect of Oral Iron Supplementation on Cognitive Function among Children and Adolescents in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.|published=2022-Dec-15|authors=Chen Z, Yang H, Wang D, Sudfeld CR, Zhao A, Xin Y, Chen JC, Fawzi WW, Xing Y, Li Z|journal=Nutrients|] 
It’s important to note that when iron supplements are taken to treat IDA, it usually takes about 3 months to replenish iron stores, and hemoglobin levels will increase gradually in the first month of supplementation.[reference|url=https://pubmed.ncbi.nlm.nih.gov/37209050|title=Iron Preparations in the Management of Iron Deficiency Anemia in Infants and Children: A Systematic Review and Meta-Analysis.|published=2023-Sep-15|authors=Arulparithi CS, Arunbabu T, Manjani S|journal=Indian Pediatr|]

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