Iron

Iron is an essential mineral most well known for its role in oxygenation, allowing blood to carry oxygen from one tissue to another. While it does not appear to have many potential roles as a supplement in excess it seems quite beneficial to supplement to maintain levels.

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Summary

All Essential Benefits/Effects/Facts & Information

In Progress


This page on Iron is currently marked as in-progress. We are still compiling research.



Iron is an essential dietary mineral found in a wide variety of food products, highly present in some plant sources such as cereal grains and legumes but most well known for being a component of meat (due to the iron in meat, under most situations, being better absorbed and used by the body).

Iron serves as a major cofactor in the body and an integral part of many enzymes, and also serves as a part of something called heme; heme binds to iron, allows it to carry oxygen, and proteins with a heme group are called hemoproteins; the most famous of which are erythrocytes (red blood cells). As such, having iron in your diet at sufficient levels allows your red blood cells to deliver oxygen to your tissues whereas a lack of dietary iron impairs this function leading to the consequences of less oxygen in tissues (primarily fatigue).

The state of not having enough iron in your body is called iron-deficiency anemia, and is treated by iron supplementation or increasing iron in your diet. This is the major reason iron is a dietary supplement and, perhaps, one of the only reasons to consider iron supplementation. Beyond the ability to support the function of hemoproteins, which is vitally important (yet wholly dependent on whether or not you get enough iron in your diet) iron does not seem to have many other major supplemental benefits that would make it worth being a dietary supplement.

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Things To Know

Things to Note

  • Iron supplementation may irritate the stomach, and while it is unavoidable in some people it can be lessened when taken with a bit of food and liquid

How to Take

Recommended dosage, active amounts, other details

Supplementation of iron should only be considered in relation to dietary iron intake, aiming for an 'ideal dose' close to the Recommended Daily Allowance (RDA) values for iron and with the sum of supplementation and diet being close to (more information can be found in the Recommended Intake section below):

  • 8 mg for men and women who do not menstruate

  • 15 mg for women who are menstruating and are before the age of 19

  • 18 mg for women who are menstruating and are after the age of 19 and menstruating

  • 27 mg for pregnant women

  • 10 mg for women who are lactating

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1Sources and Composition

1.1. Biological Significance

Iron is a mineral with high presence on the earth existing as approximately 4.7% of the earth's crust itself[1] with some essential functions in almost every organism known to exist with the exception of some species of bacteria.[2][1] This near-ubiquitous necessity is due to how iron is a mineral that works well as an enzyme cofactor for, or at least a component of, numerous enzymes vital for life; it's importance for humans is also related to this, and also to it's role in a blood component known as heme which is required to deliver oxygen to tissues.[3][1]

Outside of hemoproteins, iron can also exist in what are known as iron-sulfur clusters (ISCs) that are involved in over 200 different enzymes or proteins[4] and, similar to hemoproteins, exist in essentially all forms of life including eukaryotes,[5] bacteria,[6] and even plants.[7] When it comes to humans these proteins have been associated with energy production, existing in the mitochondria, and seem to be associated with mitochondrial diseases such as Friedreich Ataxia.[8][9]

Finally, due to the conversion of iron between the reduced form (ferrous) and the oxidized form (ferric) iron itself can induce oxidative stress in the body. While beneficial effects can occur from this action, due to the insolubility of iron then an excess of 'free iron' can damage proteins and cells.[10][11]

Iron is associated with proteins and serves a general function of either carrying oxygen or causing oxidative damage (for the purpose of initiating various cellular processes), but due to iron working through inducing oxidative stress it also exists in forms that can cause unnecessary damage to cells when iron regulation is thrown into disarray

1.2. Recommended Intake

Recommended iron intake, according to the Institute of Medicine,[12] is as follows:

  • For infants below six months of age, an adequate intake (AI) of 0.27 mg iron is recommended. This can be achieved with breast milk or with specialized infant formulations, and positions by both the Canadian Paediatric Society[13] and the American Academy of Pediatrics[14] have suggested infants fed little to no breast milk may require some manner of fortification.

  • For infants aged between 7 to 12 months the Estimated Average Intake (EAR) is 6.9 mg with the Recommended Daily Allowance (RDA) at 11 mg, with the large increase thought to be associated with an increased capacity of the body to store iron safely and increasing body mass

  • For children between the ages of 1 to 8 years the values of the Estimated Average Intake and Recommended Daily Allowance remain similar, if not a bit lower. The EAR is set at 3 mg for children 1-3 years of age and 4.1 mg for 4-8 years while the RDA is 7 mg and 10 mg respectively

  • For youth between the ages of 9-18 the EAR and RDA take a sex-based difference due to menstruation, with males being recommended an RDA of 8 mg of iron before the age of thirteen and 11 mg of iron between the ages of fourteen and eighteen. For females after the age of fourteen who are menstruating this number increases to 15 mg, with a recommendation that females under the age of fourteen who are menstruating to increase intake by around 2.5 mg (resulting in an intake of 13.5 mg)

  • For adults over the age of 19 the RDA remains constant throughout the lifetime of males at 8 mg a day. For women the RDA is similar after the age of 51 but is significantly elevated to 18 mg a day between the ages 19 and 50.

For pregnancy, the Estimated Average Requirement (EAR) and the Recommended Daily Allowance (RDA) increase to 22-23 mg and to 27 mg respectively. The state of lactation sees an EAR of 6.5-7 mg and an RDA of 9-10 mg, which are significantly lower than the recommendations for pregnancy due to a temporary lack of menstruation.

Iron recommendations follow normal trends of being related to body mass and age with a consideration for pregnancy. However, for women of reproductive age and whom are pregnant the recommended intake of iron is significantly higher, at times more than doubling, the recommended intake for men and then somewhat normalizing during lactation.

Special considerations for iron intake beyond menstruation are given in instances of strenuous exercise and frequent blood donation due to increases iron losses as well as for vegetarianism and veganism which are more likely to suffer from iron-deficiency anemia (due to less likelihood of getting iron in the diet).[12] In regards to blood donation the iron losses are in direct relation to the amount of blood given with half a liter (0.5L) of blood over the course of a year seeing an estimated increase of 0.6-0.7 mg[15] and, while accurate estimates on how much iron supplementation is needed in those who frequently partake in strenuous training, it is estimated to be between a 30-70% increase of the EAR.[12] Vegetarians and vegans have the same recommended intakes as omnivores but, due to not consuming heme iron found in meat products, are more likely to be deficient in iron due to consuming less of a more bioavailable form found in plants.

Beyond pregnancy and lactation, iron is increased during both blood donation and strenuous exercise simply because the body loses more iron. Vegetarians and vegans have similar requirements to omnivores but need to take consideration that their diets may provide less iron if measures are not taken

1.3. Deficiency

Iron deficiency in infants and children is known to be associated with cognitive impairments such as psychomotor[16] and behavioural[17] complications.


2Neurology

2.1. Depression

There does appear to be an association with high iron intake and less chance of depression as seen by a (relatively small) meta-analysis on the topic.[18]


3Cardiovascular Health

3.1. Red Blood Cells

The main function of iron in erythrocytes (red blood cells) is simply existing within the cell, in a part called heme and specifically the center of a protoporphyrin IX ring;[19] numerous different proteins may have a heme group, these proteins of which are called hemoproteins. Due to being in this position iron can become either oxygenated, bound to oxygen, or unoxygenated in a reversible manner[20] which then leads to numerous functions of red blood cells such as delivering oxygen to tissues for them to use or directly using that oxygen to influence something else in the body.[21] The ability of red blood cells to deliver and utilize oxygen is vital to health, and while many factors (such as Vitamin B12 and Folic acid) the simple provision of iron in the diet, so it can exist within heme, is perhaps the major factor.

States of the body where red blood cells are impaired in some manner (a decrease in the amount or ability of hemoglobin in red blood cells) in their ability to function are called anemias. Anemias may be genetic (Sickle Cell Anemia[22]) or due to a lack of other nutrients (Pernicious Anemia from lack of B12[23]) but the most prevalent anemia world-wide is iron-deficiency anemia caused from lack of dietary iron; either through lack of iron in the diet or an inability of the body to get the iron to red blood cells. It is treated by providing supplemental iron (preferred medical intervention), increasing dietary iron, or otherwise increasing the ability of the body to absorb and use iron[24][25][26] such as increasing the bioavailability of plant forms of iron. Iron-deficiency anemia primarily affects premenopausal women with low dietary meat intake (due to a combination of iron losses from menstration and lack of dietary iron, most commonly from meat products[27]).

Red blood cells carry oxygen to tisses in the body, and the reason they have this capacity is due to a 'heme' group that possesses iron that directly carries the oxygen. Optimal iron stores in the body support this function and, while an excess of iron does not necessarily increase this function, insufficient iron hinders it and produces one of the various forms of anemia known as Iron-deficiency anemia


4Inflammation and Immunology

4.1. Macrophages

Macrophages, an immune cell with a major role in both eliminating foreign bodies determined to be harmful and with roles in both inflammation and anti-inflammation[28] also have numerous other 'maintenance' roles in the body[29] of which include a recycling function of iron.[30] Red blood cells, like all cells, have a lifespan and eventually degrade with age (a process known as senescence) where they release their heme; this 'free heme' can damage tissue and DNA.[31] A particular type of macrophage, known as an erythrophagocytic macrophage, detects senescent red blood cells and eliminates them to limit the amount free heme from being released and damaging tissue.[32]

There exist some macrophages which detect and eliminate damaged red blood cells, which prevents the iron in red blood cells from floating around the body by itself and damaging tissue


5Peripheral Organ Systems

5.1. Female Sex Organs

A review on the topic of intermittent iron supplementation, where iron is supplemented only around the time of menstruation, found that this manner of supplementation appeared to be effective in reducing the risk of anemia (RR 0.73; 95% CI of 0.56-0.95) while increasing both ferritin and hemoglobin; however, daily supplemention of iron seemed to be better at reducing the risk of anemia despite similar improvements in hemoglobin.[27]

When it comes to reducing the risk of anemia in menstruating women, supplementing iron only around the time one menstruates does appear effective in reducing the risk of anemia but not as effective as simply taking iron supplementation each day.


6Nutrient-Nutrient Interactions

6.1. Chelation

Several plant-derived compounds have the ability to reduce iron absorption secondary to forming bonds with the iron molecule and sequestering it in the intestines, and coingestion of these compounds with iron reduces the efficacy of iron supplementation.

Curcumin (the most active component of turmeric) has shown this potential in mice only when high doses of curcumin (estimated human dose of 8-12g) are paired with low dietary iron levels;[33] diets with adequate levels of iron not being significantly hindered[33] and dietary turmeric at 500mg not having any effect in humans.[34]

The addition of 4.2g ground chili (capsicum annuum) to a meal fortified with 4mg non-heme iron showed a moderate inhibitory effect on iron absorption by 38%; this test meal being relatively high in phytic acid due to the addition of chili.[34] Rosemary (source of rosmarinic acid) has also been noted to reduce nonheme iron absorption.[35]

In regards to spices, those with high phenolic contents or those with a high phytate content may reduce iron absorption when both are ingested at the same time

Psyllium is a dietary fiber comprised of roughly equal parts soluble and insoluble fiber. While one study has noted a reduction in iron accumulation when coingested with non-heme iron[36] while other studies using prolonged supplementation of around 10g fail to find alterations in iron metabolism.[37][38][39] Psyllium has the potential to both reduce absorption of minerals via direct binding to nonheme in a manner not influenced by Vitamin C[40] while in the colon the increase in pH from psyllium has been noted to increase resorption of calcium;[41] thought to apply to other minerals as well.

While there may be an acute inhibitory effect on dietary fibers on nonheme iron absorption, the long term relevance of this is not known since fermentable dietary fibers may also increase mineral resorption from the colon

Coffee is known to inhibit iron absorption when coingested with nonheme iron,[42] potentially due to the activities of chlorogenic acid which is a known iron chelator[43] which would extend this inhibition to the dietary supplement known as Green coffee extract (a higher source of chlorogenic acid).

Other beverages that have been noted to inhibit iron absorption in a test meal include peppermint tea,[42] green tea (due to catechins[35]), black tea[42] (additional theaflavin component may play a role[44]), vervain tea,[42] lime flower tea,[42] pennyroyal tea,[42] and chamomile tea.[42]

A wide variety of beverages that are known to have a high antioxidant content, including coffee and teas from camellia sinensis such as green or black teas have some acute inhibitory effect on iron

6.2. Vitamin C

Vitamin C is known to assist the absorption of iron in the intestines. Iron that is not bound in heme (the ring associated with proteins which 'carries' it) has its absorption in the intestines[45][46] as, when ascorbate cycles back and forth between intestinal cells it reduces iron to a form more readily absorbed; this process is hindered by a lack of ascorbate availability.[47] This initial phase of assisting absorption occurs outside the intestinal cell[48] while inside the cell ascorbate assists in transferring iron to Transferrin, a transfer protein which delivers iron to cells.[49] This latter function is thought to explain[49] why instances of Scurvy (Vitamin C deficiency) is associated with degrees of iron-deficiency anemia.[50][51]

Scientific Support & Reference Citations

References

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  6. Ayala-Castro C, Saini A, Outten FW Fe-S cluster assembly pathways in bacteria . Microbiol Mol Biol Rev. (2008)
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  12. Institute of Medicine (US) Panel on Micronutrients Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc . . (2001)
  13. The Canadian Paediatric Society Meeting the iron needs of infants and young children: an update. Nutrition Committee, Canadian Paediatric Society . CMAJ. (1991)
  14. The American Academy of Pediatrics Iron Fortification of Infant Formulas . . (1999)
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