Iron Deficiency and Anemia
Iron is needed to manufacture hemoglobin, which enables red blood cells to transfer oxygen to the body's tissues. Severe or prolonged iron deficiency is the leading cause of anemia in the United States, affecting about five percent of women and two percent of men. Symptoms of iron deficiency anemia include easy fatigability, shortness of breath, dizziness, headache, coldness of hands and feet, pale skin, chest pain, weakness, and lethargy. Other symptoms can include brittle nails, swelling or soreness of the tongue, cracks in the sides of the mouth, loss of taste, an enlarged spleen, and frequent infections. Iron deficiency has also been associated with recurrent aphthous stomatitis (canker sores) (Akintoye, Dent Clin North Am 2014
). Some people with iron-deficiency anemia develop restless legs syndrome (see more about this in Benefits of Correcting Iron Deficiency below). Iron deficiency anemia can also cause irregular heartbeats (arrhythmias), a heart murmur, an enlarged heart, and heart failure (Kettaneh, Appetite 2005
; NIH, 2014
Iron deficiency is most common in menstruating women but also is commonly seen in children and pregnant women. According to the CDC
, 9.5% of women 12 - 29 years are deficient, as are 6.7% of children ages 1 to 5. There are higher rates of iron deficiency in Mexican-American children aged 1 to 5 years (11%) and in non-Hispanic black (16%) and Mexican-American women (13%) of childbearing age (12 to 49 years) when compared to other race/ethnic groups. Low iron levels also may result from excessive bleeding, burns, and hemodialysis, as well as stomach and intestinal problems. Drugs that reduce stomach acid may also impair iron absorption (see What to avoid when taking
During pregnancy, iron deficiency can result in preterm delivery and low-birth-weight babies.
Among children, iron deficiency is most common from ages 6 to 24 months, where it can cause developmental and behavioral problems. If iron deficiency is extremely severe, some of these problems can be irreversible.
Although few men are deficient in iron, 29% are at-risk for iron excess
Benefits of Correcting Iron Deficiency
Some evidence suggests that even mild iron deficiency, too mild to cause anemia, may cause fatigue and impair sports performance. Iron supplementation has been shown to reduce unexplained fatigue in women of child-bearing age
who are not anemic but have ferritin levels in the lower end of normal range (less than 50 ug/L) (ferritin is an indicator of total iron stored in the body). A 12-week study of 198 such women (ages 18 to 53) found that those who received 80 mg of iron from ferrous sulfate daily from a time-release pill experienced a 47.7% decrease in fatigue, compared to a 28.8% decrease in the placebo group — a significant difference (Vaucher, CMAJ 2012
), although there was no significant effect on anxiety or depression. Ferritin levels increased by 11.4 ug/L compared with placebo.
Among blood donors
with normal hemoglobin levels, low-dose iron supplementation (37.5 mg of iron as ferrous gluconate daily) reduces the time by more than half for hemoglobin and ferritin levels to recover after donating a unit of blood. A study showed that those receiving iron recovered most of their decrease within about 30 days versus 78 to 158 days for those not receiving iron, depending on whether their ferritin levels were initially high or low. For those getting the iron supplement, ferritin levels returned to normal within 76 days while 67% of those not receiving supplementation had not fully recovered iron stores after 168 days -- when the study ended (Kiss, JAMA 2015
). The researchers noted that although the hemoglobin decrease after donation is relatively small (about 10%) and of marginal clinical significance, for frequent donors it is important to be recovered before the next donation; suggesting that the current waiting period of 8 weeks (56 days) in the U.S. may be too short.
Verbal learning and memory
have been shown to improve when adolescent girls with iron deficiency (although not anemia) are treated with iron supplementation (Bruner, Lancet 1996
Unfortunately, among patients with heart failure
and iron deficiency, giving high-dose iron (150 mg as iron polysaccharide) twice daily for 16 weeks did not improve peak oxygen uptake nor exercise capacity (6-minute walking distance) and only minimally improved iron levels (a 3% increase). A possible reason for the failure (which was not expected, as iron given intravenously in such patients raises iron by about 70%), was abnormally high blood levels in these people of hepcidin
, an iron regulatory hormone that lowers iron levels by reducing iron absorption and trapping iron in while blood cells and liver cells (Lewis, JAMA 2017
People with low or deficient levels of iron may be more likely to suffer from restless legs syndrome
. Guidelines from the American Academy of Neurology advise that taking 65 mg of iron (from 325 mg ferrous sulfate) and 200 mg vitamin C (to help with iron absorption) twice daily may improve symptoms in individuals with restless legs syndrome who have ferritin levels below 75 ng/mL (Winkelman, Neurology 2016
). This recommendation is based on a small study that gave a similar treatment (although half the vitamin C: 100 mg twice daily) to older men and women with low-normal blood ferritin levels (15 - 75 ng/mL) for three months. The severity of restless legs symptoms decreased by an average of 10 points on a scale of 0 to 40, while it decreased by just 1 point among those who took a placebo (Wang, Sleep Med 2009
). Overall quality of life, however, did not improve in either group. Taking the iron increased blood ferritin levels from an average of 40 ng/mL to 65 ng/mL. Be aware that restless legs syndrome may also occur as a result of hereditary hemochromatosis (a disorder in which too much
iron is absorbed from the diet and ferritin blood levels can get too high
) and this treatment would not seem appropriate in such a situation (Cotter, Ther Clin Risk Manag 2006
Iron supplements have shown some promise for reducing the dry cough caused by drugs
in the angiotensin-converting enzyme inhibitor family (ACE inhibitors).
A small study of iron in children with ADHD
showed improvement in some symptoms comparable to that with stimulant medicines (Konofal,Pediatr Neurol 2008
A lower risk of suffering PMS
(premenstrual syndrome) has been associated with a high intake of iron (over 20 mg per day) from supplements or plant-based foods (as opposed to meats) (Chocano-Bedoya, Am J Epidem 2013
). Compared to women with the lowest daily intakes of iron (median of 9.4 mg) from these sources, the risk of PMS was reduced by 29% among those with a median intake of 21.4 mg, and by 36% among those with a median intake of 49.2 mg. Interestingly, the same study found that women consuming higher amounts of potassium from their diet (median intake of 3,717 mg daily) had a higher
risk of PMS than those consuming less potassium.
for information about the forms of iron in supplements and dosage.