For the brain, iron levels may need to be just right

January, 2012

Iron-enriched baby formula improves cognitive development when infants have low iron levels, but harms development when iron levels are already high. Teenage iron levels are linked to white matter integrity in adulthood.

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).

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