Johnston and Stiffler

Savanna Johnston and Haylee Stiffler

Nutrition and Health of Iron
SCH 202 02
November 18, 2019

As an element, iron is the fourth most abundant element by mass in the earth’s
crust and has a molecular weight of 55.845 amu (1). Iron is one of only four vitamins or minerals
that must be listed on nutrition labels in the United States as mandated by the Food and Drug
Administration (2). Because of this, it’s obvious that iron is important to our health, but what
exactly is it doing for us?
In our body iron is only stable in two forms, known as ferric iron, Fe3+, and ferrous iron,
Fe2+. Most of the iron that we consume is in the ferric form, which must be reduced by enzymes
found on the brush border of the duodenum, such as duodenal cytochrome b (3). After iron
absorption occurs it’s transferred through the body by binding to the glycoprotein transferrin (4).
Once in the blood iron can be used in many ways. Most of the iron absorbed is found in
hemoglobin, which is responsible for oxygen transfer, or as myoglobin, which is responsible for
oxygen storage in muscle tissues throughout the body. The remainder of iron is stored as ferritin
and is found in the spleen, liver, and bone marrow (4). Iron is also found in the brain, where it
plays a role as a cofactor for the enzyme tyrosine hydroxylase, which is responsible for
dopamine synthesis (5).
Dopamine is a neurotransmitter that plays a major role in neurological functions as well
as mental health. It’s commonly associated with depression, anxiety, schizophrenia, restless leg
syndrome and Parkinson’s disease (5). Tyrosine hydroxylase (TyrH) uses tetrahydrobiopterin
and oxygen to convert the amino acid tyrosine to L-dihydroxyphenylalanine (L-DOPA), a
precursor to dopamine, as well as other catecholamines norepinephrine and epinephrine (5).
TyrH is a member of the hydroxylase family, it uses diatomic oxygen and reduced biopterin as
well as an iron atom, which is held in place in the active site by two histamine residues and a
glutamate residue, in its reactions. For the reaction to proceed iron must be in its ferrous state (6).
TyrH is considered the rate-limiting enzyme of catecholamine synthesis, when one of the
catecholamines is needed TyrH is activated to increase DOPA synthesis (6). As a cofactor, iron
is used in the active site to activate molecular oxygen, during the catalyzation reaction the
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ferrous iron is oxidized further but is converted back into ferrous iron by the end of the catalytic
cycle (6). One way that DOPA production is regulated is through the oxygenation state of iron.
As previously mentioned, the reaction is only able to proceed when iron is in its ferrous state, to
prevent the reaction from occurring oxygen can oxidize ferrous iron to ferric iron. Iron must then
be reduced before DOPA production is able to proceed again (6).
The human body also requires iron to synthesize oxygen transport and storage proteins,
known as hemoglobin and myoglobin. Each of these proteins contain a ferrous iron molecule
which binds to oxygen via its unshared electron pairs (2). Without the presence of iron in these
molecules, the oxygen would not be able to bind and be transported or stored throughout the
body, resulting in oxygen deficiency in the various tissues of the body.
Due to irons importance for bodily functions it’s recommended that most people consume
between 10mg and 20mg per day, although this recommendation does vary based on age, dietary
requirements, and whether or not they menstruate (4). Those who menstruate are recommended
to consume more iron than people who don’t due to increased iron loss in the blood. People who
don’t eat meat are also recommended to consume 1.8 times more iron than those who do (4).
There are two different types of iron that come from food sources, known as heme iron and
nonheme iron. Heme iron comes from meats and seafood, while nonheme iron comes from
vegetables and iron fortified foods such as cereals (4). The amount of iron consumed does not
equate to the amount of iron absorbed, instead iron absorption ranges from 5% to 35% of the
amount consumed. The variation is due to the type of iron, meaning heme or nonheme, as well
the presence of other vitamins or minerals in the body, some of which can increase iron
absorption (7).
Maintaining iron homeostasis in the body is essential to overall health and wellbeing.
Despite this, there are no active excretory mechanisms for iron (3). There are small amounts lost
as a result of skin and gastrointestinal cell exfoliation, and large amounts are lost during
menstruation (3). Due to this, iron levels are controlled by the regulation of absorption in the
duodenum, allowing for the body to adjust based on need (3). Even though this relationship
between iron absorption and the needs of the body exists there is still the possibility of having
excess or insufficient iron stores, which can be detrimental to overall bodily health.
Iron deficiency is incredibly common, it’s estimated to affect at least two billion people
worldwide, making it one of the most common nutrient deficiencies (8). The most at risk
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populations include young children and pregnant and postpartum women due to the increased
iron demand associated with growth and pregnancy (8). Since iron comes from food sources,
people who follow diets that have limited, or no, meat products are also at a higher risk to
develop iron deficiency. This could be vegetarians, vegans, people who live in areas where
eating meat isn’t culturally common, or people that don’t have access to meat or iron fortified
foods.
Anemia is a disorder that’s most commonly caused by iron deficiency and is
characterized by the blood not having enough healthy red blood cells (9). Red blood cells contain
hemoglobin, which is responsible for transporting oxygen to the various bodily tissues.
Symptoms of anemia can include fatigue, pale skin, dizziness, cold hands, and brittle nails (9).
Restless leg syndrome is also now being recognized as a symptom of iron deficiency,
particularly during pregnancy (10). This symptom is most likely related to the role of iron in
dopamine production, while the others are most likely due to the lack of oxygen being delivered
to the tissues.
Iron deficiency has also been linked to anxiety, depression, and attention deficit, which
can continue after the iron deficiency has been corrected with supplements (5). Evidence shows
that this is likely due to the role iron plays in dopamine synthesis, although this is not the definite
cause. Patients with these disorders have also been shown to have lower levels of zinc and
selenium (5). This information points to the possibility of general malnutrition causing some
types of mood disorders, which would include iron malnutrition.
Diagnosing iron deficiency anemia requires blood testing, which a medical provider will
use to observe any abnormalities in various blood levels or the appearance of blood cells. It’s
common for red blood cells to be smaller and paler than normal when a patient has iron
deficiency anemia (9). Hematocrit, hemoglobin, and ferritin levels are also commonly lower than
usual and would be beneficial for a provider to know in order to properly diagnose and treat the
patient (9). If the bloodwork results are indicative of iron deficiency anemia the provider may
then request additional testing to look for internal bleeding that could be the underlying cause.
Additional tests could include an endoscopy, colonoscopy, or ultrasound (9).
Iron supplements are commonly given as an over the counter or prescription remedy to
iron deficiency, when available. When taking iron supplements, it’s recommended to take
vitamin C supplements as well, as vitamin C has been shown to increase iron absorption with the
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assistance of the enzyme duodenal cytochrome b. This enzyme participates in electron transfer
between ferric iron and intracellular vitamin C, which reduces ferric iron to ferrous iron so that it
can be absorbed (3). When treating iron deficiency it can also be beneficial to look at the
underlying cause of the deficiency. While insufficient iron in the diet is a common cause of iron
deficiency, it can also be due to blood loss, pregnancy, or underlying medical conditions that
damage the ability of the intestines to absorb nutrients, such as celiac disease (9). In these cases,
taking iron supplements would be beneficial, but it may also be necessary to treat the underlying
cause as well. Due to this, when iron deficiency is due to menstrual blood loss medical
practitioners may prescribe hormonal contraceptives to decrease iron loss (9).
When diagnosed and treated properly and in a timely manner the condition will usually
resolve without any long-term complications. Although iron deficiency should be a relatively
easy fix, it’s often overlooked by medical practitioners in the developed world. In contrast, iron
deficiency anemia can result in life-long consequences in developing countries where people
may not have easy access to medical care, iron fortified foods, or supplements (10).
Evidently, iron is an incredibly important nutrient that affects physical and mental health.
Without it our bodies are not able to function optimally, which can lead to detrimental health
consequences. Solving the crisis of iron deficiency can be difficult, especially when considering
how the most at risk populations are at risk due to a lack of access to health care and nutrition.
Increasing access to iron fortified food and health care would be the best solution to nutrient
deficiency, although this isn’t exactly an easy solution. Outside of this, educational programs
could be beneficial for areas where people have access to meat products but don’t commonly eat
them, as meat is a major source of iron. Obviously, this solution isn’t perfect either since many
people have cultural, religious, or dietary restrictions that would prevent them from eating meat.
These problems make a solution difficult to find, but it’s very important that a solution is found
so that global health can be improved.
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References

1. Iron - Element information, properties and uses: Periodic Table.

https://www.rsc.org/periodic-table/element/26/iron (accessed Nov 16, 2019)
2. McMurry, J.; Ballantine, D. S.; Hoeger, C. A.; Peterson, V. E. Fundamentals of
general, organic, and biological chemistry, 8th ed.; Pearson: Boston, 2017; pp
618, 578
3. Gulec, S.; Anderson, G. J.; Collins, J. F. Mechanistic and Regulatory Aspects of
Intestinal Iron Absorption. American Journal of Physiology-Gastrointestinal and
Liver Physiology 2014, 307(4).
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4. National Institutes of Health Office of Dietary Supplements Iron Fact Sheet,

https://ods.od.nih.gov/factsheets/Iron-HealthProfessional/(Accessed Oct. 8th,
2019)
5. Daubner, S. C.; Le, T.; Wang, S. Tyrosine Hydroxylase and Regulation of Dopamine
Synthesis. Archives of Biochemistry and Biophysics 2011, 508(1).
6. Frantom, P. A.; Seravalli, J.; Ragsdale, S. W.; Fitzpatrick, P. F. Reduction and
Oxidation of the Active Site Iron in Tyrosine Hydroxylase: Kinetics and
Specificity. Biochemistry 2006, 45(13).
7. Abbaspour, N.; Hurrell, R.; Kelishadi, R. Review on Iron and Its Importance for
Human Health. Journal of Research in Medical Sciences 2014, 19(2).
8. World Health Organization. The World Health Report: Reducing Risks, Promoting
Healthy Life. Geneva: World Health Organization; 2002. pp 52 - 54
9. Mayo Clinic, Iron Deficiency Anemia,
https://www.mayoclinic.org/diseases-conditions/iron-deficiency-anemia/symptom
s-causes/syc-20355034(accessed Oct. 17th, 2019)
10. Miller, J. L. Iron Deficiency Anemia: A Common and Curable Disease. Cold Spring
Harbor Perspectives in Medicine 2013, 3(7).