Iron

A number of studies have found that iron deficiency in children and adolescents is associated with lower scores of cognitive tests. Moreover, there is some evidence that iron deficiency during infancy has persistent effects on cognition that are still evident in adolescence. This may be exacerbated for those with poor family conditions.

While iron deficiency was once presumed to exert most of its deleterious effects only if it reached the level of anemia, it has more recently become recognized that many organs show negative changes in functioning before there is any drop in iron hemoglobin concentration. A large U.S. national study found iron deficiency in 3% of children (6-16), and 8.7% of girls aged 12 to 16.

There has been less research done on the effects of iron deficiency on cognition in adults, but there are indications that iron deficiency is associated with poorer attention and working memory in both young and older women.

A post-mortem study of five Alzheimer's and five control brains has revealed the presence of iron-containing microglia in the subiculum of the Alzheimer's brains only. The subiculum lies within the hippocampus, a vital memory region affected early in Alzheimer's. None of the brains of those not diagnosed with Alzheimer's had the iron deposits or the microglia, in that brain region, while four of the five Alzheimer's brains contained the iron-containing microglia.

The microglia were mostly in an inflamed state. Growing evidence implicates brain inflammation in the development of Alzheimer's.

There was no consistent association between iron-laden microglia and amyloid plaques or tau in the same area.

Obviously, this is only a small study, and more research needs to be done to confirm the finding. However, this is consistent with previous findings of higher levels of iron in the hippocampi of Alzheimer's brain.

At the moment, we don't know how the iron gets into brain tissue, or why it accumulates in the subiculum. However, the researchers speculate that it may have something to do with micro-injury to small cerebral blood vessels.

This is an interesting finding that may lead to new treatment or prevention approaches if confirmed in further research.

http://www.eurekalert.org/pub_releases/2015-07/sumc-sss072015.php

The hippocampus is damaged early in Alzheimer’s, while the thalamus is generally unaffected until the late stages. Brain imaging of the hippocampus and the thalamus in 31 patients with Alzheimer's and 68 healthy controls has revealed increased levels of iron in the hippocampus of those with Alzheimer’s, but not in the thalamus. Moreover, this increased iron was associated with tissue damage in patients with Alzheimer's but not in the healthy older individuals.

The findings support the view that iron accumulation is a factor in the development of Alzheimer's disease. It’s theorized that the buildup of tau and amyloid-beta is a response to the destruction of myelin. Myelin, and the oligodendrocytes that produces it, have the highest levels of iron of any cells in the brain.

http://www.eurekalert.org/pub_releases/2013-08/uoc--uss082013.php

Raven, E.P. 2013. Increased Iron Levels and Decreased Tissue Integrity in Hippocampus of Alzheimer’s Disease Detected in vivo with Magnetic Resonance Imaging. Journal of Alzheimer’s Disease, 37 (1), 127-136

Following on from the evidence that Alzheimer’s brains show higher levels of metals such as iron, copper, and zinc, a mouse study has found that amyloid plaques in Alzheimer’s-like brains with significant neurodegeneration have about 25% more copper than those with little neurodegeneration. This is consistent with a human study showing very high levels of copper in Alzheimer’s plaques.

Iron, though doubled in Alzheimer’s brains compared to controls, was not significantly different as a function of neurodegeneration, and zinc showed very little difference.

The findings suggest that the cellular control of copper is altered in some way in Alzheimer’s brains, while the increase in oxidized iron suggests it might be useful as a biomarker for the early diagnosis of Alzheimer’s.

http://www.eurekalert.org/pub_releases/2013-08/ip-elo082113.php

[3555] Bourassa MW, Leskovjan AC, Tappero RV, Farquhar ER, Colton CA, Van Nostrand WE, Miller LM. Elevated copper in the amyloid plaques and iron in the cortex are observed in mouse models of Alzheimer's disease that exhibit neurodegeneration. Biomedical Spectroscopy and Imaging [Internet]. 2013 ;2(2):129 - 139. Available from: http://dx.doi.org/10.3233/BSI-130041

Iron deficiency is the world's single most common nutrient deficiency, and a well-known cause of impaired cognitive, language, and motor development. Many countries therefore routinely supplement infant foods with iron. However, a new study suggests that, while there is no doubt that such fortification has helped reduce iron deficiency, it may be that there is an optimal level of iron for infant development.

In 1992-94, 835 healthy, full-term infants living in urban areas in Chile, took part in a randomized trial to receive iron-fortified formula from 6 months of age to 12 months. A follow-up study has now assessed the cognitive functioning of 473 of these children at 10 years of age. Tests measured IQ, spatial memory, arithmetic achievement, visual-motor integration, visual perception and motor functioning.

Those who had received iron-fortified formula scored significantly lower than the non-fortified group on the spatial memory and visual-motor integration tests. Moreover, their performance on the other tests also tended to be worse, although these didn’t reach statistical significance.

There was no difference in iron level between these two groups (at age 10), and only one child had iron-deficiency anemia.

The crucial point, it seems, lies in the extent to which the infants needed additional iron. Children who had high iron levels at 6 months (5.5%, i.e. 26 infants) had lower scores at 10 years if they had received the iron-fortified formula, but those with low 6-month iron levels (18.4%; 87 infants) had higher scores at 10 years.

Further research is needed to confirm these findings, but the findings are not inconsistent with the idea that iron overload promotes neurodegenerative diseases.

In another longitudinal study, brain scans have revealed that teenage iron levels are associated with white matter fiber integrity.

The study first measured iron levels in 615 adolescent twins and siblings, and then scanned their brains when they were in their early twenties. Myelin (white matter) contains a lot of iron, so the strong correlation between teenage iron level and white matter integrity in young adulthood is not unexpected.

The correlation was stronger between identical twins that non-identical twins, suggesting a genetic contribution. Again, not unexpected — the transport of iron around the body is affected by several genes. One particular gene variant, in a gene that governs cellular absorption of transferrin-bound iron, was associated with both high iron levels and improved white matter integrity. This gene variant is found in about 12-15% of Caucasians.

The vital missing bit of information (because it wasn’t investigated) is whether this gene variant is associated with better cognitive performance. Further research will hopefully also investigate whether, while it might be better to have this variant earlier in life, it is detrimental in old age, given the suggestions that iron accumulation contributes to some neurodegenerative disorders (including Alzheimer’s).

A new study finds out why curcumin might help protect against dementia, and links two factors associated with Alzheimer’s and Parkinson’s diseases: DNA damage by reactive oxygen species (ROS), and excessive levels of copper and iron in parts of the brain. It turns out that high levels of copper or iron help generate large numbers of ROS and interfere with DNA repair.

While small amounts of iron and copper are vital, these are normally bound by proteins. However, when there’s too much, it can overwhelm the proteins and the result is "free" iron or copper ions circulating in the blood, able to initiate chemical reactions that produce reactive oxygen species. Moreover, the free copper and iron also interferes with the activity of two enzymes that repair DNA, NEIL1 and NEIL2.

However, the curry spice curcumin binds to iron and copper and was extremely effective in protecting the NEIL enzymes from the metals.

Hegde, M.L., Hegde, P.M. , Rao, K.S.J. & Mitra, S. 2011. Oxidative Genome Damage and Its Repair in Neurodegenerative Diseases: Function of Transition Metals as a Double-Edged Sword. Journal of Alzheimer's Disease , 25 (1), 183-198.

A study involving 676 children (7-9) in rural Nepal has found that those whose mothers received iron, folic acid and vitamin A supplementation during their pregnancies and for three months after the birth performed better on some measures of intellectual and motor functioning compared to offspring of mothers who received vitamin A alone. However, there was no significant benefit for those whose mothers received iron, folic acid and zinc (plus vitamin A), or multiple micronutrients.

A negative effect of adding zinc is consistent with other research indicating that zinc inhibits iron absorption. Interestingly, new “ground-breaking” research demonstrates further the complexity of iron’s effects on the body. The researcher argues that many neurodegenerative diseases (such as Alzheimer’s) are partly caused by poorly bound iron, and it is vital to consume nutrients which bind iron and prevent the production of the toxins it will otherwise produce.

Such nutrients include brightly-colored fruits (especially purple) and vegetables, and green tea.

It’s also argued that Vitamin C is only beneficial if iron is safely bound, and if it’s not, excess Vitamin C might be harmful.

Older news items (pre-2010) brought over from the old website

Iron supplements might harm infants who have enough

U.S. infant formulas typically come fortified with 12 mg/L of iron to prevent iron-deficiency anemia, although Europe generally uses a lower amount. A study of 494 Chilean children has now showed that those who received iron fortified formula in infancy at the 12 mg level used in the U.S. lagged behind those who received low-iron formula in cognitive and visual-motor development by age 10 years. While most children who received the higher level formula did not show lower scores, the 5% with the highest hemoglobin levels at 6 months showed the poorest outcome. Adversely affected children scored 11 points lower in IQ and 12 points lower in visual-motor integration. This suggests that those who are not deficient in iron are adversely affected by giving them too much. It seems likely that more than 5% of U.S. infants will have high hemoglobin levels. More research is needed to confirm this finding.

Castillo, M. & Smith, J.B. 2008. Poorer developmental outcome at 10 years with 12 mg/L iron-fortified formula in infancy. Paper presented May 5 at the Pediatric Academic Societies annual meeting in Honolulu.

http://www.eurekalert.org/pub_releases/2008-05/uom-ism043008.php

Iron-deficient infants have lower cognitive scores at 19, especially in lower socioeconomic levels

Another study has come out finding that teenagers who were iron-deficient as infants continue to lag behind their peers in cognitive test scores, with a wider gap for children at lower socioeconomic levels. The study of 185 children from an urban area in Costa Rica, found that among children from middle-class families, initial scores on cognitive tests were eight points apart, 101.2 for those with iron deficiency and 109.3 for those with sufficient iron levels, and this gap remained at eight or nine points through 19 years. However, for those in lower socio-economic classes, initial scores that were ten points apart (93.1 for iron-deficient infants and 102.8 for those with normal iron levels) had widened by 19 years to 25 points (70.4 vs. 95.3). The finding points to the snowball effect of early failure.

[1145] Lozoff B, Jimenez E, Smith JB. Double Burden of Iron Deficiency in Infancy and Low Socioeconomic Status: A Longitudinal Analysis of Cognitive Test Scores to Age 19 Years. Arch Pediatr Adolesc Med [Internet]. 2006 ;160(11):1108 - 1113. Available from: http://archpedi.ama-assn.org/cgi/content/abstract/160/11/1108

http://www.eurekalert.org/pub_releases/2006-11/jaaj-idi110206.php

Impact of iron deficiency in infancy continues into adolescence

A new study has found that teens who suffered iron deficiency as infants are likely to score lower on cognitive and motor tests, even if that iron deficiency was identified and treated in infancy. The study followed 191 children. Those who were diagnosed with severe, chronic iron deficiency when they were 12-23 months old and were treated with iron supplements, lagged behind their peers in both motor and mental measures. The difference, moreover, actually increased over time. The iron-deficient infants scored about six points lower on cognitive tests at age 1-2 years, and 11 points lower at age 15-18 years. The gap was even more pronounced for children of families with low socioeconomic status, lower stimulation in the home or mothers lower in IQ. For children with good iron status, family conditions did not seem to affect their cognitive test scores. The researcher stressed that the children were not generally malnourished. Moreover, it must be emphasized that these children received treatment for their iron deficiency, yet still showed continuing ill effects, pointing to the need to prevent the deficiency occurring in the first place.

Lozoff, B. 2004. Longitudinal Analysis of Cognitive and Motor Effects of Iron Deficiency in Infancy. Presented at the Pediatric Academic Societies' annual meeting in San Francisco May 3.

http://www.eurekalert.org/pub_releases/2004-05/uom-iis050404.htm

American Academy of Pediatrics information on iron intake for infants: http://aappolicy.aappublications.org/cgi/content/full/pediatrics;104/1/119

Even moderate iron deficiency affects cognitive performance

A new study involving 149 young women (aged 18 to 35, average age 21), has found that iron supplementation significantly improved attention, short-term and long-term memory, and performance on cognitive tasks in those who were deficient in iron, even if not classified as anemic. On the baseline test, women who were iron deficient but not anemic completed the tasks in the same amount of time as iron sufficient women of the same age, but they performed significantly worse. Women who were anemic both performed significantly worse and took longer, with length of time increasing with degree of anemia. However, 16 weeks of iron supplementation markedly improved both scores and time to complete the task.
While iron deficiency was once presumed to exert most of its deleterious effects only if it had reached the level of anemia, it has more recently become recognized that many organs show negative changes in functioning before there is any drop in iron hemoglobin concentration. Iron deficiency is thought to occur in 9 – 11% of women of reproductive age and 25% of pregnant women. In non-industrialized countries, the prevalence of anemia is over 40% in non-pregnant women and over 50% for pregnant women and children aged five to 14.

Murray-Kolb, L., Beard, J. & Whitfield, K. 2004. presented at Experimental Biology 2004, in the American Society of Nutritional Sciences' scientific program.

http://www.eurekalert.org/pub_releases/2004-04/foas-mid040404.php

U.N. prescribes nutrient-fortified foods

A new U.N. survey says the brainpower of many developing countries has diminished because of a shortage of the right vitamins. To fight the problem, the United Nations is prescribing artificially fortified foods: soy sauce laced with zinc, "super salt" spiked with iron, cooking oil fortified with vitamin A. The report claimed a lack of iron lowered children's IQs by an average five to seven points, while a deficiency in iodine cuts it 13 more points. The report was produced by the Micronutrient Initiative and the United Nations Children's Fund.
http://www.micronutrient.org/

Iron deficiency may affect maths achievement in children and teens

A U.S. national study of 5,398 children aged 6 to 16 found iron deficiency in 3% of the children overall, and 8.7% of girls aged 12 to 16 (7% without anemia). Average math scores for iron-deficient children with or without anemia were about six points lower than those with normal iron levels. Among adolescent girls, the difference in scores was more than eight points. Previous research has linked iron-deficiency anemia with lower developmental test scores in young children, but there is less information on older children and on iron deficiency without anemia. It is suggested that this finding may help explain why the female superiority in maths at younger ages reverses itself in adolescence.

Halterman, J.S., Kaczorowski, J.M., Aligne, C.A., Auinger, P. & Szilagyi, P.G. 2001. Iron Deficiency and Cognitive Achievement Among School-Aged Children and Adolescents in the United States. Pediatrics, 107 (6), 1381-1386.

http://www.pediatrics.org/cgi/content/abstract/107/6/1381

Anemia linked to impaired thinking in older adults

For older adults, anemia has long been linked to fatigue, muscle weakness and other physical ailments. But a new study suggests it may also be an independent risk factor for executive-function impairment. The study examined 364 women between 70 and 80 years old, of whom some 10% had mild anemia. Those with anemia were four to five times more likely to perform worst on the executive function tests.

[708] Chaves PHM, Carlson MC, Ferrucci L, Guralnik JM, Semba R, Fried LP. Association Between Mild Anemia and Executive Function Impairment in Community-Dwelling Older Women: The Women's Health and Aging Study II. Journal of the American Geriatrics Society [Internet]. 2006 ;54(9):1429 - 1435. Available from: http://dx.doi.org/10.1111/j.1532-5415.2006.00863.x

http://www.eurekalert.org/pub_releases/2006-09/jhmi-aab091306.php