Iron

Overview

Iron plays a role in many biochemical pathways. The primary functions of iron involve oxygen transport within blood and muscle, electron transfer in relation to the cellular uptake of oxygen, and the conversion of blood sugar to energy. Iron is also a part of many enzymes that are involved with making new cells, amino acids, hormones, and neurotransmitters.

Iron exists in various forms in the body: in functional forms (in hemoglobin and in enzymes) and in transport and storage forms (ferritin, transferrin, and hemosiderin).

Dosage Info

Dosage Range

10-50mg daily. Under the supervision of a healthcare practitioner doses between 50-100mg, three times a day for a limited time are commonly used for iron deficiency.

Most Common Dosage

15mg daily.

200mg of elemental iron
= ~1.66g ferric pyrophosphate
= ~1.66g ferrous gluconate
= ~1g ferrous sulfate
= ~0.66g ferrous sulfate, dried
= ~0.61g ferrous fumarate
= ~0.42g ferrous carbonate, anhydrous

Dosage Forms

Capsules, tablets, time-released capsules, liquid, and injectable iron drug products (Rx only).

Adult RDI

10mg
20mg

Adult ODA

18mg

RDA

• Infants < 6 months: 0.27mg (Adequate Intake, AI)
• Infants 7-12 months: 11mg
• Children 1-3 years: 7mg
• Children 4-8 years: 10mg
• Children 9-13 years: 8mg
• Males 14-18 years: 11mg
• Females 14-18 years: 15mg
• Males >19 years: 8mg
• Females 19-50 years: 18mg
• Females >51 years: 8mg
• Pregnancy: 27mg
• Lactation 14-18 years: 10mg
• Lactation >19 years: 9mg

Interactions and Depletions

Interactions

• Bile acid sequestrants
• H-2 receptor antagonists
• penicillamine
• Tetracyclines
• Fluoroquinolone Antibiotics
• calcium
• magnesium
• manganese
• zinc
• phosphorus
• ascorbic acid

Depletions

• Salicylates
• indomethacin
• neomycin
• stanozolol

Active Forms

Ferrous sulfate, ferrous gluconate, ferrous fumerate, ferrous glycinate, ferric ammonium citrate, and heme iron.

Absorption

There are two methods for iron absorption in the human intestinal tract, one for heme-bound iron from meat and a different mechanism for inorganic or non-heme (ferrous) iron. The absorption of heme iron is much more efficient; approximately 25 percent of ingested heme iron is absorbed, while only 5 to 10 percent of inorganic iron is absorbed. Iron is released from hemoglobin by the action of the enzyme heme oxygenase. Inorganic iron must be in the ferrous (Fe⁺²) state in order to be absorbed. Reducing compounds like ascorbate increase iron absorption by keeping it in the ferrous state.

Toxicities & Precautions

General

When the body’s iron stores are full, the body absorbs less iron. Therefore, iron toxicity is relatively rare, but it can occur, usually due to an accidental overdose of iron tablets. Therefore, OTC and prescription iron-containing products must be packaged in child-resistant safety packaging.

Side Effects

Side effects are possible with any dietary supplement. This dietary supplement may cause nausea, vomiting, constipation and black stools. (1) Also, iron-containing liquids may temporarily stain the teeth. (2) Dilute the liquid to reduce this possibility. When iron-containing drops are given to infants, the membrane covering the teeth may darken.

Functions in the Body

Oxygen Transport:

The major function of iron is for oxygen transport by hemoglobin. Hemoglobin is the oxygen-carrying protein in red blood cells. The heme portion of hemoglobin contains four atoms of iron. Iron picks up the oxygen in the lungs where the concentration is high. Iron binds the oxygen and then transports it to the tissues and releases it wherever it is needed.

Oxygen Storage:

Myoglobin is an iron-containing protein in muscles that acts as an oxygen acceptor and an oxygen storage reservoir in muscle.

Immune System:

Iron is one of the substances that is necessary for optimal immune response. (3)

Fatty Acid Metabolism:

Necessary for the synthesis of the amino acid carnitine, which plays a role in the metabolism of fatty acids.

Energy Production:

Much of iron’s functional activity in electron transport and energy production has to do with its ability to convert back and forth between its reduced or ferrous state (Fe⁺⁺), and its oxidized ferric state (Fe⁺⁺⁺). This is how oxygen is either held or released.

Liver Detoxification:

Plays a role in the cytochrome P450 liver detoxification enzymes. (4)

Neurotransmitters:

Part of the enzyme that initiates the synthesis of the neurotransmitters serotonin and dopamine.

Collagen and Elastin:

The synthesis of collagen and elastin require iron.

Clinical Applications

Pregnancy

Iron deficiency anemia is common during pregnancy; (5) deficiency during the first trimester contributes to reduced size and birthweight of the infant. (6)

Restless Legs Syndrome

Sufferers frequently have a dramatic reduction in symptoms with iron supplementation. (7)

Menorrhagia

Iron deficiency resulting from heavy menstruation can be corrected with iron supplementation. (8) , (9)

Immune Function

Elevated iron status increases susceptibility to infections. (10)

Symptoms and Causes of Deficiency

Menstrual bleeding is the most common cause of iron deficiency. About 80 percent of the iron in the body is in the blood, so iron loss is greatest whenever blood is lost. Menstruating women require approximately twice as much iron intake as men to replace their monthly losses. Individuals at risk include infants, adolescent girls, pregnant women, menstruating women, people with bleeding ulcers, and vegetarians.

Iron deficiency anemia is the classic condition where red blood cells contain less hemoglobin and consequently carry less oxygen. Symptoms of iron deficiency include: anemia, weakness, fatigue, skin pallor, headache, hair loss, labored breathing after exertion, spooning of fingernails, brittle nails, and greater susceptibility to infections. Pagophagia is a term referring to an individual who deliberately consumes large quantities of ice. This condition is related to iron deficiency and is completely resolved with low level iron supplementation. Hypochlorhydria: Gastric hydrochloric acid is necessary for iron absorption. A low production of gastric hydrochloric acid, which occurs often in the elderly, can lead to iron deficiency. The use of antacids and drugs that alter gastric acidity inhibit iron absorption. Complexing agents, such as phytates, oxalates and phosphates, form insoluble iron complexes, which reduce absorption. Vitamin E also inhibits the absorption of iron. This is generally not a cause of iron deficiency, but it is not advisable to take supplemental doses of iron and vitamin E at the same time. Diarrhea, intestinal inflammation, or other conditions that increase intestinal motility will also reduce absorption. Iron deficiency can cause hair loss. Athletes may be more susceptible to iron loss. Those with Crohn’s Disease are more susceptible to iron deficiency. (11)

Dietary Sources

Liver is by far the richest iron-containing food. Other good sources of iron-rich foods include organ meats, fish, and poultry. Dried beans and vegetables are the best plant sources, followed by dried fruits, nuts, and whole grain breads and cereals. Fortification of cereals, flours, and bread with iron has contributed significantly to daily dietary iron consumption.

References

1. View Abstract: Roth JL, Pugh LC. Side effects of alternative iron supplementation: a pilot study. Pa Nurse. Jun1998;53(6):16-8.
2. View Abstract: Warner RR, Myers MC, Burns J. Analytical electron microscopy of chlorhexidine-induced tooth stain in humans: direct evidence for metal-induced stain. J Periodontal Res. Jul1993;28(4):255-65.
3. View Abstract: Ahluwalia N, Sun J, Krause D, Mastro A, Handte G. Immune function is impaired in iron-deficient, homebound, older women. Am J Clin Nutr. Mar2004;79(3):516-21.
4. View Abstract: Cederbaum AI. Iron and CYP2E1-dependent oxidative stress and toxicity. Alcohol. Jun2003;30(2):115-20.
5. View Abstract: Schwartz 3rd WJ, et al. Iron Deficiency Anemia in Pregnancy. Clin Obstet Gynecol. Sep1995;38(3):443-54.
6. Doyle W, et al. The Association Between Maternal Diet and Birth Dimensions. J Nutr Med. 1990;1:9-17.
7. View Abstract: O’Keeffe ST, Gavin K, Lavan JN. Iron Status and Restless Legs Syndrome in the Elderly. Age Ageing. May1994;23(3):200-03.
8. View Abstract: Arvidsson B, et al. Iron Prophylaxis in Menorrhagia. Acta Obstet Gynecol Scand. 1981;60(2):157-60.
9. View Abstract: Barr F, et al. Reducing iron deficiency anaemia due to heavy menstrual blood loss in Nigerian rural adolescents. Public Health Nutr. Dec1998;1(4): 249-57.
10. View Abstract: Foster SL, Richardson SH, Failla ML. Elevated iron status increases bacterial invasion and survival and alters cytokine/chemokine mRNA expression in Caco-2 human intestinal cells. J Nutr. May2001;131(5):1452-8.
11. View Abstract: Lomer MC. Intake of dietary iron is low in patients with Crohn’s disease: a case-control study. Br J Nutr. 2004 Jan;91(1):141-8.