Uses

Iron-deficiency anemia

Anemia is a state of having too few red blood cells and/or too little hemoglobin, the molecule that carries oxygen, in the red blood cells. Symptoms of anemia include fatigue, pale skin, weakness, and possibly dizziness. Anemia can be caused by many things, and iron supplementation is appropriate only when the cause of the anemia is iron deficiency. Iron deficiency can result from too little iron in the diet, blood loss, or excessive blood cell destruction (caused by some drugs and certain disease conditions).

Low iron stores

Low iron stores precede anemia and may be associated with tiredness, since iron is involved in energy production. A blood test for ferritin, an iron storage molecule in the blood, can detect low iron stores even when anemia is not present. Without the blood test, you may not know whether your iron stores are deficient. Tiredness is a symptom of low iron stores, but tiredness can have many other causes. Iron supplementation can raise iron stores.

Restless Leg Syndrome

Restless leg syndrome (RLS), characterized by an uncontrollable urge to move one’s legs, especially at night and worsening with rest, is highly correlated with low ferritin in the cerebral spinal fluid (CSF).¹ Iron is a necessary cofactor for tyrosine hydroxylase, an enzyme involved in the formation of dopamine, a neurotransmitter involved in controlling movement. CSF ferritin may or may not be correlated with serum ferritin. Even people with the genetic disease hemochromatosis (iron overload and hence high serum ferritin) can have low CSF ferritin—and RLS.² Such individuals apparently have a problem with iron transport into the CSF. However, for a person with RLS and low serum ferritin (i.e., iron deficiency), iron supplementation may relieve RLS. Before taking iron supplementation to relieve suspected RLS, it is best to have low iron status confirmed by a serum ferritin test.

Choosing an Iron Supplement

Two factors of concern in choosing an iron supplement are its bioavailability (how much of it you can absorb) and the side effects it may cause.

Factors Affecting Iron Absorption

The major factors affecting the amount of iron you will absorb from the amount you take in are:

• Your iron status
• Your stomach acid production
• Inhibitors or enhancers of absorption in your diet
• The form of iron, i.e., the compound the iron is in

If you are iron deficient, you will absorb a greater portion of the iron you consume than if you are not. This is a protective mechanism of the body, since iron is absolutely necessary for life, yet it is toxic in very high amounts.

Stomach acid enhances the solubility of iron in foods and iron from non-heme supplements (see below for information on heme and non-heme forms of iron) and thereby enhances its absorption. When stomach acid production is impaired, such as by drugs that prevent acid production (e.g., Prilosec^® or Nexium^®), iron absorption is reduced.

Normal compounds in the diet such as phytates in grains and beans, oxalates in spinach and many other vegetables, and tannins in tea and coffee can bind to iron and make it unavailable for absorption. Vitamin C and citric acid, on the other hand, enhance the absorption of iron.

Calcium, magnesium, and zinc can interfere with iron absorption. Therefore, it is recommended that supplements of those minerals be taken at a different time than iron supplements, such as at bedtime.

The form of iron that is best absorbed is heme iron—up to about 30% may be absorbed. “Heme” refers to the iron-containing portion of the hemoglobin molecule. Iron in heme form is found in meats, fish, and poultry, with the highest levels occurring in red meats, including organ meats, such as liver. Heme is absorbed from the intestine by a different route than are other forms of iron, and its absorption is not influenced by other factors in the diet or by stomach acid.^{3 4} According to Michael Murray, author of Encyclopedia of Nutritional Supplements, the net amount of iron absorbed from 3 milligrams of heme iron is the same as that absorbed from 50 milligrams of non-heme iron such as ferrous succinate.⁵

Absorption of inorganic iron salts (e.g., ferrous sulfate—the most commonly prescribed form) is low—typically less than 10%. When an inorganic iron salt is taken with a meal, its absorption is decreased or enhanced by the dietary factors mentioned above. It is often recommended that ferrous sulfate, ferrous gluconate, and ferrous fumarate be taken on an empty stomach. However, taking them with food reduces their side effects (see below for information on side effects).

Absorption of iron in the form of an amino acid chelate (e.g., iron glycinate) is thought to be better than absorption of iron in the form of an inorganic salt, although there is disagreement among researchers on the interpretation of data. According to one theory, amino acid chelates of iron are absorbed intact and their absorption is not reduced by dietary inhibitors. However, other researchers believe that the iron from amino acid chelates is absorbed by the same mechanism as that used by inorganic salts and is subject to the same dietary inhibitors.

Manufacturers of liquid iron formulas claim that iron absorption from liquids is greater than iron absorption from tablets. Consequently, they claim, one needs to take less iron to achieve comparable results. However, there does not appear to be much published experimental evidence to support or refute these claims. The form of iron in liquid formulas can be any of those found in tablets, such ferrous gluconate, ferrous lactate, or an amino acid chelates.

Side Effects of Iron Supplements

Ferrous sulfate is notorious for the side effects it can cause at doses used to treat anemia: constipation or diarrhea, stomach pain or cramping, nausea, vomiting, and heartburn. A benign side effect is black stools, which are caused by unabsorbed iron. Gentler iron compounds can be substituted for ferrous sulfate to effectively overcome anemia. Amino acid chelates are reported to cause few or no stomach or intestinal problems. Heme likewise is benign. With respect to unwanted side effects, iron supplements could be ranked in the following manner:

heme < amino acid chelates < ferrous fumarate < ferrous gluconate < ferrous sulfate

How Much To Take

Recommended daily iron intakes are shown in the following table.⁶

Children, 7 to 12 months        11 mg/day

Children, 1 to 3 years                7 mg/day

Children, 4 to 8 years              10 mg/day

Children, 9 to 13 years              8 mg/day

Males, 14 to 18 years              11 mg/day

Females, 14 to 18 years          15 mg/day

Males, over 19 years                 8 mg/day

Females, 19 to 50 years          18 mg/day

Females, over 51 years             8 mg/day

Pregnancy                               27 mg/day

Lactation                                   9 mg/day

These recommendations are daily intakes from all sources combined (diet and supplements, if taken) for people to maintain adequate iron status. They assume the average bioavailability of iron from the diet to be about 18%.⁷ For treating anemia in adolescents and women, the Centers for Disease Control (CDC) recommends 60 milligrams of elemental iron once or twice daily.⁸ It should be noted that smaller amounts of heme iron will be needed to overcome anemia, since the bioavailability of iron from heme is greater than from other sources.

Amount of Elemental Iron

Most intake recommendations indicate the amount of elemental iron one should take. Unfortunately, prescriptions often specify an amount of an iron compound to take, without saying how much elemental iron is in the compound. For example, a prescription of 325 milligrams of ferrous (aka, iron) sulfate refers to the weight of the entire ferrous sulfate compound, not just the elemental iron in it. Ferrous sulfate contains only 20% elemental iron. Therefore, 325 milligrams of ferrous sulfate contains approximately 65 milligrams of elemental iron. Fortunately, supplement product labels indicate the amount of elemental iron in each serving in the Supplement Facts panel. For example, an iron supplement may say each capsule contains 25 mg of iron (as iron bisglycinate chelate), which tells us the weight of the elemental iron (25 mg), but not the weight of the iron bisglycinate chelate compound. Once you’ve calculated how much elemental iron you’ve been prescribed, you can just match up that amount with the amount of iron indicated on the product label of the compound you want to take.  It is absolutely critical that you know the amount of elemental iron in a compound if you wish to substitute a different form of iron for the one you’re taking or have been prescribed.

Cautions

Iron overload

The body has no natural means of eliminating iron excesses once they have been absorbed. Iron excess can cause serious liver and heart problems. The body’s natural reduction in rate of absorption when iron status is high helps prevent accumulation of excesses, but it is insufficient to prevent iron overload if incoming iron is too great.

Adult men and post-menopausal women rarely need iron supplementation. Since iron overload is a concern, men and post-menopausal women should be sure that their multivitamin/mineral supplement does not contain iron unless they have been diagnosed specifically with iron deficiency anemia.

For anyone diagnosed with iron deficiency anemia, the source of the problem (e.g, blood loss) should be determined and corrected. Supplementation with iron is then appropriate for restoring optimal iron status.

Interference with drugs

Iron can interfere with the effectiveness of certain antibiotics (e.g., tetracycline, penicillamine, quinolones), methyldopa (used for treating high blood pressure), levodopa (used to treat Parkinson’s disease), and bisphosphonates (drugs for treating osteoporosis, such as Fosamax^®).

References

Mizuno S et al. CSF iron, ferritin and transferring levels in restless legs syndrome. J Sleep Res 2005; 14:43-47.

Barton JC et al. Hemochromatosis and iron therapy of restless legs syndrome. Sleep Med 2001; 2(3):249-251.

Shayeghi M et al. Identification of an intestinal heme transporter. Cell 2005; 122(5):789-801.

“Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese Molybdenum, Nickel, Silicon, Vanadium, and Zinc.” National Academies Press website, 2000 (May 2008), http://www.nap.edu/openbook.php?record_id=10026&page=293.

Murray MT, Encyclopedia of Nutritional Supplements (New York: Three Rivers Press, 1996), 211.

“Dietary Supplements Fact Sheet: Iron,” Office of Dietary Supplements, NIH website, 2007 (30 May 2008), <http://dietary-supplements.info.nih.gov/factsheets/iron.asp&gt;

“Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese Molybdenum, Nickel, Silicon, Vanadium, and Zinc.” National Academies Press website, 2000 (May 2008), <http://www.nap.edu/openbook.php?record_id=10026&page=315&gt;.

“Recommendations to Prevent and Control Iron Deficiency in the United States”, Centers for Disease Control website, April 1998 (May 2008), <http://www.cdc.gov/mmwr/preview/mmwrhtml/00051880.htm>.