Restless Legs: The Iron Connection

The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 8 No. 3 • July 2005

It is a commonplace that the history of civilisation is largely the history of weapons … And though I have no doubt exceptions can be brought forward, I think the following rule would be found generally true: that ages in which the dominant weapon is expensive or difficult to make will tend to be ages of despotism, whereas when the dominant weapon is cheap and simple, the common people have a chance. Thus, for example, tanks, battleships, and bombing planes are inherently tyrannical weapons, while rifles, muskets, longbows, and hand grenades are inherently democratic weapons. A complex weapon makes the strong stronger, while a simple weapon—so long as there is no answer to it—gives claws to the weak.
— George Orwell, “You and the Atomic Bomb”
British Labour Party journal Tribune, October 19, 1945
Wherever the real power in a Government lies, there is the danger of oppression. In our Governments the real power lies in the majority of the Community, and the invasion of private rights is chiefly to be apprehended, not from acts of Government contrary to the sense of its constituents, but from the acts in which the Government is the mere instrument of the major number of the constituents.
— James Madison, in a letter to Thomas Jefferson
October 17, 1788
Madison did not see that minorities could exploit majorities when the benefits of government action to those minorities were huge and the costs to each individual in the majority were small.
— John Samples, Cato Policy Report
March/April 2001
A standing military force with an overgrown Executive will not long be safe companions to liberty. The means of defense against foreign danger have been always the instruments of tyranny at home.
— James Madison, at the Constitutional Convention
June 29, 1787
Our peculiar security is in the possession of a written Constitution. Let us not make it a blank paper by construction.
— Thomas Jefferson

Restless Legs: The Iron Connection

Before you rush out to buy the latest expensive prescription drug for “restless legs,” you might consider that one cause of this condition is iron deficiency.1 The prescription drugs used to treat restless legs stimulate the function of dopaminergic neurons. Iron deficiency is known to cause a reduction in dopaminergic activity (as well as a rise in serum prolactin).2

Many people these days have reduced their intake of red meat, the best dietary source of iron. White meat (such as poultry) contains much less. Moreover, those who eat a diet rich in polyphenols—as are found in fruits, in vegetables, and in green, black, and oolong tea, etc.—may be absorbing much less than the quantity of iron they ingest because of the potent iron-chelating properties of many polyphenols (such as quercetin). If you are eating a diet like this and have developed restless legs, it is quite possibly due to iron deficiency.

In a recent study,1 rats were fed diets that were either iron-deficient (ID) or iron-adequate (CN). Another group of ID rats was given iron supplements (IR). Studies were done on the dopamine, serotonin, and noradrenaline transporter binding in various brain areas. The results showed that ID male rats (but not ID females) had a decrease of 20–40% in dopamine transporter binding in the nucleus accumbens, caudate putamen, and substantia nigra. ID males also had a 20–30% reduction in serotonin transporter binding in the nucleus accumbens, olfactory tubercle, and colliculus, while ID females had 15–25% increased serotonin transporter binding in the olfactory tubercle, zona incerta, anteroventral thalamic nucleus, and vestibular nucleus. [It is possible that this increased serotonin transporter binding is linked to increased sensitivity to depression in females, at least in those who are iron-deficient, since the serotonin reuptake inhibitors, such as fluoxetine (Prozac®), inhibit the serotonin transporter.] Iron deficiency reduced binding to the noradrenaline transporter in the locus ceruleus and anteroventral thalamic nucleus in ID and IR males but not females. Some, but not all, of the changes induced by iron deficiency were reversed by iron supplementation.

The authors state, “This experiment extends our knowledge to include the olfactory tubercle as a tissue sensitive to iron deficiency. This might implicate iron deficiency in endocrinological difficulties such as hyperprolactinemia.” Prolactin is regulated by dopamine. High levels of prolactin stimulate the growth of breast and prostate tissue; they may thus be a risk factor for developing breast and prostate cancers and would certainly stimulate the growth of such cancers.

We became interested in the connection between iron deficiency and restless legs when Sandy developed the latter condition. It has been completely eradicated with daily RDA-level iron supplementation. Iron supplements should be taken at separate times from other supplements because of the possibility of chemical interactions with vitamin C, resulting in free radical generation, or with irreversible binding to polyphenols, especially quercetin. We suggest using ferrous gluconate; iron-EDTA chelates produce hydroxyl radicals very efficiently in the presence of vitamin C, and ferrous sulfate can be quite irritating.


  1. Burhans et al. Iron deficiency: differential effects on monoamine transporters. Nutr Neurosci 8(1):31-8 (2005).
  2. Barkey et al. Characterization of the hepatic prolactin receptors induced by chronic iron deficiency and neuroleptics. Eur J Pharmacol 122:259-67 (1986).

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