Restless legs syndrome (RLS) appears to possibly be caused by carbon monoxide buildup in leg muscles. Here's why I think that could be the case:
1) Everyone's body makes endogenous carbon monoxide in small amounts. The endogenous carbon monoxide is a product of the breakdown of heme, a cofactor containing iron that is found primarily in animal products.
2) There appears to be a weak association between a heme oxygenase (which produces carbon monoxide) gene and RLS.
3) When we rest in a horizontal position, we are lowering arterial O2 (oxygen) pressure in the legs, which can cause more carbon monoxide to move from blood to the muscles. This effect should be even more pronounced during pregnancy due to the temporarily increased weight on the legs when standing; pregnancy is associated with increased risk of RLS. Compression stockings would help keep arterial pressure high; many RLS sufferers find that using compression stockings lessens their symptoms.
4) Carbon monoxide binds to myoglobin--"The oxygen carrying and storage protein of muscle, resembling hemoglobin but containing only one subunit and one heme as part of the molecule (rather than the four of hemoglobin), and with a molecular weight approximately one quarter that of hemoglobin," per an online medical dictionary--in the muscles. Thus, those who are already deficient in iron would tend to suffer more from higher levels of carbon monoxide interfering with myoglobin in the muscles. RLS has long been found associated with low stores of iron in the body.
5) The primary (and almost only) treatment for carbon monoxide poisoning is oxygen therapy. Peripheral hypoxia in the legs is associated and correlated in degree with RLS.
6) The most well-known symptom related to RLS is involuntary movement of the leg muscles. This movement could be the body trying to get more oxygen to the leg muscles in order to alleviate carbon monoxide buildup in the legs. Moving muscles take in more oxygen than resting ones.
7) Severe RLS and ischemic stroke are correlated. Carbon monoxide poisoning also correlates with an increased risk of ischemic stroke. This is a point in support of the hypothesis that endogenous carbon monoxide poisoning is behind RLS.
8) Dopamine agonists lessen RLS symptoms. Dopamine is also used to increase arterial pressure in patients with hypotension (low blood pressure). This is another point in support of the hypothesis, for increasing arterial pressure can be expected to help prevent the movement of carbon monoxide from blood into muscles.
Does my theory point to ways to treat RLS? I see a few, many of which have already been studied and shown positive effects:
- Increase oxygen inhalation at night. RLS is associated with reduced oxygen saturation and sleep-related breathing disorders.
- Look into ways to increase arterial pressure at night. Obviously, compression stockings can help do that. Also, progressive exercise programs that increase overall strength help with RLS, perhaps because having stronger cardiac and rib-cage-connected muscles increases arterial pressure and/or oxygen inhalation.
- Massage leg muscles. It can contribute to an increase in muscle blood volume.
- Dopamine agonists, as mentioned above in #8.
- Don't be deficient in iron.
- Don't over-consume heme, a form of iron from animal products that is the primary source of endogenous carbon monoxide.
- Don't be deficient in vitamin E, which in the form of d, alpha-tocopheryl acetate, appears to relieve RLS leg cramps. I suspect this is partially due to alpha-tocopherol's inhibition of lipid peroxidation, which results in production of endogenous carbon monoxide.
- Perhaps acizol, a new zinc-containing medication for acute carbon monoxide poisoning, would be helpful for RLS. No research has been done on this, though.
- Hydroxocobalamin combined with Vitamin C shows promise as a treatment for carbon monoxide poisoning, per a rat study published last year. If carbon monoxide is connected to RLS, then hydroxocobalamin and Vitamin C supplements together might help with RLS.