Article on Restless Legs Syndrome

http://well.blogs.nytimes.com/2008/12/17/voices-of-restless-legs-syndrome/

There's an article in the NY Times on restless legs syndrome. A significant percentage of cases of primary restless legs syndrome are supposedly due to poor transport of iron into the basal ganglia, in the brain, and, more specifically, different groups of dopaminergic neurons in the basal ganglia (http://scholar.google.com/scholar?q=restless+legs+syndrome+iron+dopamine&hl=en&lr=). I forget which ones. Nonheme iron is supposedly a component of the D2 dopamine receptor, and iron repletion increase the Bmax, like the density of binding sites, of D2 dopamine receptors on dopaminergic neurons in the brain. The drugs used to treat RLS are D2 dopamine receptor agonists. There's research on low serum iron being linked to various differences in the responses, such as a tendency to produce akathisia, like a sort of extreme inner restlessness, to dopaminergic drugs. Restless legs syndrome is also common in elderly people, and that type of akathisic response would probably be more likely to occur in elderly people, too, regardless of the person's serum iron level. Researchers have used high-dose iron in some studies, but I don't think it works consistently. Experts in iron metabolism generally set the no observed adverse effect level of iron supplementation (or maybe dietary + supplementation) for nonheme iron at 40-45 mg per day, and there's one study showing that 50 mg of supplemental nonheme iron per day is equivalent to a diet high in red meat (in terms of iron provision). They've also used absurdly high-dose folic acid, like 30 mg/d, to treat restless legs syndrome, even though that dose would probably be unsafe in the long term. The key point is the kinetic aspect of iron delivery, and the dopaminergic changes probably depend more on serum iron than serum ferritin. There's only so much to be done with iron, given that long-term intakes above the NOAEL are potentially damaging. Folic acid supplementation also tends to deplete iron by lowering serum ferritin, especially at doses of 4-5 mg/d.