Deficiency of Iron Viewed as Greater Threat
A series of recent studies show that iron-deficiency anemia--one of the most common nutritional disorders in the world--may have more long-term health effects than doctors have ever suspected.
Until recently, it was often presumed that iron-deficiency anemia had few deleterious health effects unless it was severe enough to harm the functioning of the heart or lungs, Dr. Betsy Lozoff, a pediatrician at Case Western Reserve University School of Medicine in Cleveland, told a recent symposium on nutrition, children and health sponsored by the New York Academy of Medicine.
But preliminary results from recent studies in humans and animals suggest that iron deficiency may produce many health problems, particularly when it occurs in infancy and early childhood. Among the more serious health consequences, Lozoff said, are deficits in motor coordination and risk for lower learning potential.
Common Nutritional Disorder
Iron-deficiency anemia--which is caused by insufficient iron in the diet--is one of the most common nutritional disorders in the world. An estimated 1 billion people worldwide--most of them infants, children and women--are thought to be affected by the nutritional disorder.
It has a peak prevalence among infants, affecting an estimated 25% of all babies, Lozoff told the symposium. In the United States, however, perhaps only 3% to 8% of babies are affected.
Approximately 20% of adult men and 35% of adult women in the world are also anemic--most as a result of iron deficiency, she said.
At greatest risk of iron deficiency are those caught in poverty and disadvantaged social conditions. “Iron-deficiency anemia is very preventable,” Lozoff said. “The United States has made dramatic inroads into prevention by encouraging breast-feeding (of infants) and the use of iron-fortified foods.”
Poor Urban Areas of U.S.
Despite these advances, iron-deficiency anemia remains a problem both in poor, urban areas of the United States and in many underdeveloped nations throughout the world.
Iron is important for health because it is a key constituent of hemoglobin--the molecule that allows red blood cells to carry oxygen to cells throughout the body. In addition, research shows that iron plays an important role in brain and central nervous system functions. Iron begins to be stored in the brain before birth and continues accumulating until early adulthood.
There are varying degrees of iron deficiency, which can range from a reduction in the amount of stored iron--with no effect on hemoglobin or other iron-containing compounds throughout the body--to anemia, the most severe form of iron deficiency.
With the more severe forms, a host of brain functions can be affected--one reason iron deficiency in infancy and childhood may pose far more serious health consequences than deficiency that occurs later in life.
Animal studies conducted by Moussa Youdim and his colleagues at the Technion Israel Institute of Technology in Haifa, Israel, have shown that rats who sustained early iron deficiency had persistent learning and behavioral deficits. Exactly how iron deficiency may cause these behavioral effects is not completely understood, but early findings suggest that they are promoted by changes in key brain neurotransmitters, such as dopamine, serotonin and GABA (gamma-aminobutyric acid.)
Age-Related Effects
For example, Youdim and his colleagues have found that iron-deficient rats show “a significant and selective reduction” in the amount of one type of dopamine receptor in the brain. Important age-related effects have been shown in these studies as well. For instance, the effects of iron deficiency were not reversible when they occurred in 10-day-old rats but were reversed when they occurred in older animals. Other iron-deficiency changes have been documented in the serotonin system, which is responsible for mood, activity and the sleep-wake cycle, and in the GABA system, which inhibits other brain chemicals.
Preliminary findings from human studies also point to similar effects of iron deficiency. Five separate studies by researchers in different countries have documented “clinically and statistically significant lower mental test scores among anemic infants prior to treatment,” Lozoff reported.
In one study of 191 healthy Costa Rican infants ages 12 to 23 months, Lozoff and her colleagues discovered that “infants with moderate iron-deficiency anemia were found to have lower mental and motor test scores than appropriate controls.”
“And infants with mild anemia received lower motor scores but not mental scores,” she told the conference.
Lower Scores for Anemics
For example, moderately anemic infants (whose serum hemoglobin was less than 10) scored an average eight points lower on mental tests than did comparable babies who were not anemic. On tests measuring motor ability, the group of anemic infants scored an average 10 points lower than the non-anemic babies.
The Costa Rican study results are important because all the babies came from the same community, helping to ensure that population biases that often plague studies of this sort were minimized.
“An extensive set of background variables relating to birth, general nutritional status, lead level, family background, home environment and parental IQ failed to reveal any factor other than iron-deficiency anemia that might explain the findings,” Lozoff said.
Other studies suggest that iron-deficient children may experience adverse emotional effects. For example, a study of iron-deficient infants in Guatemala found that these babies were unduly fearful, unhappy, tired, tense, hesitant and withdrawn, compared with control infants who were not anemic.
Study of Chilean Infants
The extent of iron deficiency also seems to help dictate how severely affected a child will be, as shown by a study of Chilean infants soon to be published in the journal Pediatrics. Dr. Tomas Walter and his colleagues at the University of Chile tested the iron levels of a group of infants at 9 months of age and again at 1 year. Walter also tested the developmental level of the babies. He found that 39 infants with iron-deficiency anemia had significantly lower mental and motor scores than either 127 iron-deficient, but non-anemic infants or 30 control babies with normal iron stores.
There are also indications that iron deficiency may also place youngsters at greater risk for chronic problems. The Costa Rican children in Lozoff’s study and the children from Walter’s study in Chile are being reassessed 5 to 5 1/2 years after their iron deficiency was discovered. “Preliminary results from both samples indicate that the formerly anemic children are still testing lower in mental and motor functions,” Lozoff reported.
“It is worrisome,” she said, “that the majority of anemic infants did not show improvements with iron therapy.”
It may be that iron deficiency, or some closely associated but as yet unidentified factor, “places children at risk for lasting developmental disability,” she said.
Different for Older Children
The story may be different for children who become anemic at an older age. Studies in Indonesia and Thailand point to higher achievement test scores with iron supplements. These results suggest that “behavior changes in older children, in contrast to those in infants, may improve with iron therapy,” Lozoff said.
Whether iron deficiency can produce chronic impairment in adolescents and adults is not known. That research, Lozoff told the symposium, “is too limited and flawed at the present time to support any conclusions.”
But the bottom line of all this research, she said, “provides increasingly persuasive arguments for intensifying efforts to prevent and treat iron-deficiency anemia.”
