Restless Legs Syndrome
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Metformin and RLS

One of my cousins said that she has had RLS for the past 3 years. She gave

me an article that discusses RLS and Metformin (a diabetes drug) I thought

that I would pass this along because she wants to know if anyone else has

had this same problem. She is on Metformin and has been for 3 years. Here

is the article or whatever you want to call it.,RLS/?a=s

I hope that the link works. Thank you for your input.

13 Replies

Link didn't work for me.


Link doesnt work, but i have been researching metformin and all i can find is it seems to cause leg cramps for alot of people, cant find anything which says RLS and metformin....


Metformin allegedly elevates levels of dopamine? So you would think that it would be of some benefit? But it's not nice to fool mother nature. Eventually she will figure out a way under-sensitize the brain to the excess dopamine created by the metformin and possibly dopamine in general, resulting in a brain that demands ever more dopamine. When it doesn't get that dopamine well, you know the rest.


Have you a link which tells us that Metformin allegedly elevates the levels of dopamine, so we can read it, please.


J Endocrinol. 2005 Jan;184(1):233-9.

Insulin sensitizing drugs increase the endogenous dopaminergic tone in obese insulin-resistant women with polycystic ovary syndrome.


The American Journal of Psychiatry, VOL. 169, No. 8

Editorial | August 01, 2012

Metformin as a Treatment for Antipsychotic Drug Side Effects: Special Focus on Women With Schizophrenia

Robert C. Smith, M.D., Ph.D.

Am J Psychiatry 2012;169:774-776. doi:10.1176/appi.ajp.2012.12050591

On the basis of previous studies of the effectiveness of metformin in restoring menstruation in women with polycystic ovarian syndrome (11) and in nonpsychotic patients with amenorrhea (12), Wu and colleagues designed a double-blind study of metformin (1000 mg/day) or matched placebo in antipsychotic-treated schizophrenia patients with amenorrhea. The authors report that 66% of the metformin-treated patients, compared with only 2% of the placebo patients, resumed menstruation during the 6-month study, and the mean time for restoration of menstruation was 2 months. Metformin also decreased levels of prolactin, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) and significantly decreased weight, insulin levels, and insulin resistance in these patients. Logistic regression analysis suggested that decreases in body weight, insulin resistance, and levels of prolactin, LH, and FSH were all related to the drug's therapeutic effect of restoring menstruation, although the specific contribution of these effects to the mechanism by which metformin restores menstruation is not clear. Many antipsychotic drugs exert some of their biological or clinical effects by interfering with dopamine transmission through blockade of postsynaptic dopamine receptors; this is believed to be an important mechanism through which these drugs raise prolactin and other hormone levels. Metformin has been shown to increase dopaminergic tone in patients with polycystic ovarian syndrome (13), and this may be one of its mechanisms of action in the clinical effects reported here. It is also important to note that there were no differences in side effects between the metformin and placebo groups, which indicates that metformin was a safe treatment as well as an efficacious one.


What does treating the effects of antipsychotic drugs have to do with RLS? Really would appreciate some updated links, since you are sharing info that so far, as I can see , as nothing to do with RLS specifically. WE really have no idea, nor do the experts, whether dopamine is huge connection to RLS. Many researchers are actually getting off the dopamine connection, or at least saying that it cannot possibly be the only cause. So, some more evidence of what you are trying to explain would help. And, as you said, lostinamerica (LIA for short) ;) "if you can't explain simply then you don't understand it well enough." Einstein quote. And, let's face it no one understands RLS, we only have theories, plus WE know what works best for us on an individual basis.


Hey, I'm responding to Jaynielynne and trying to find a connection between RLS and metformin. Don't blame the messenger. Plus, go to PA site where they've found that Metformin causes b12 deficiency. LIA stands for Little know It All. That would me.

You have been to hell and back, I have not, so I must bow to your knowledge always. I have many benign, albeit annoying conditions. I only danced with the RLS for a short while. It is evil incarnate. It is mentally and physically the most outrageous, ridiculous, bizarre (you stand up and it goes away) agonizing form of torture I have ever known. And I went through barbed wire and down hill on an ATV in Costa Rica and got over a hundred stitches unanaesthized. ( I was high for a week on the endorphins that were released from that little near death experience.) It was a walk in the park compared to RLS. The Israelis use sleep deprivation as a very successful measure of torture. I understand why. RLS is beyond sleep deprivation however.

I truly believe it is a genetic variable that we all have (and an environmental trigger). How the heck did that gene survive millions of years of evolution? Those of us who were awake were less likely to be eaten by a saber toothed tiger? I would rather be eaten alive.

With that said I can joke about it because a few days into my restless body I read a post (possibly from here) about you know what. At this point I am addicted to it. I barely even have restless leg yet I still take it. Iron is not a supplement, it is a drug when it is coursing through your brain and giving birth to dopamine. I become so relaxed and have such a feeling of well being that I don't even want to fall asleep. IT IS NOT THE CURE, I KNOW. I also know that I have robust iron stores but that my body is greedily keeping it in those stores and away from my brain. I have to break free of the iron addiction because I have a bad feeling that it is only making things worse.

Plus, everyone's available iron drops at night, but not everyone gets RLS? And everyone's body withholds iron during times of infection and other attacks, yet not everyone gets RLS when this happens? Why are some people so sensitive to these drops? Or is that our bodies have Master Ironkeepers (called hepcidin)? Do our brains (and probably other organs) really get no iron? Are we the blue medal winners of iron sequestration. My sister in law is a rheumatologist and has no idea what I'm talking about, all she knows is lots of her RA patients have RLS and lots don't. One strange thing she said to me is that NONE of her patients sleep well, RLS or not. Sad.

Time to inject my brain with !@#$.


That doesnt help much if at all.


The only info on this at all, besides is a diabetes discussion forum, and only one person said they had any issues with RLS, and everyone else said they did not. The % on treato .com is 0.03% on any posts that have to do with metformin. I have never ever heard of this, does not mean it can't be true, but cannot find anything that is less than 8 or 9 years old. It says maybe for "insulin resistant" people, but that is all. And, there was no difference in a small study that compared metformin and placebo. Do we have anything newer? The metformin info on RLS in my search RLS runs out after 4 links , after you get past the "RLS cure" ads. So not much info out there, so I would say that the jury is way out on this one, and not sure if you are saying metformin causes RLS or helps it, "lostinamerica". Would like to see more of what you have been looking at. Not sure what polycystic ovarian syndrome has to do with RLS and metformin, except maybe a small dopamine connection, and dopamine is not always the answer, as we all know.


Forget metformin for now, read this from that always reliable source, Wikipedia/Human Iron Metabolism. Remember, hepcidin is the iron GATEKEEPER and the ENEMY

Bacterial protection[edit]

In response to a systemic bacterial infection, the immune system initiates a process known as iron withholding. If bacteria are to survive, then they must obtain iron from their environment. The harder they have to work to get iron, the greater a metabolic price they must pay. That means that iron-deprived bacteria reproduce more slowly. So our control of iron levels appears to be an important defense against most bacterial infections; there are some exceptions however. TB resides within macrophages which are an iron rich environment and Borrelia burgdorferi utilises manganese in place of iron. People with increased amounts of iron, like people with hemochromatosis, are more susceptible to some bacterial infection.[4]

Although this mechanism is an elegant response to short-term bacterial infection, it can cause problems when inflammation goes on for longer. Since the liver produces hepcidin in response to inflammatory cytokines, hepcidin levels can increase as the result of non-bacterial sources of inflammation, like viral infection, cancer, auto-immune diseases or other chronic diseases. When this occurs, the sequestration of iron appears to be the major cause of the syndrome of anemia of chronic disease, in which not enough iron is available to produce enough hemoglobin-containing red blood cells.[1]


Now read this: I think what they are saying is that hepcidin is significantly higher in late onset (secondary) RLS as compared to controls, while it is lower with primary when compared to controls. The point here I think is that no matter how much iron we take or have or supplement, once the gatekeeper gets its greedy little hands on it, it ain't going nowhere. So don't always think in terms of iron levels (40, 50, 75) think in terms of "iron management" or more importantly "iron sequestration."

Is ferroportin–hepcidin signaling altered in restless legs syndrome?☆

Stacey L. Clardy


Restless legs syndrome (RLS) is a neurological disorder characterized by a strong urge to move the legs. Sufferers of RLS often experience chronic sleep deprivation, due to the characteristic worsening of symptoms both when at rest and during the night. MRI data, autopsy studies, and a consistent decrease in CSF ferritin all suggest that early-onset RLS is associated with insufficient iron in the brain. In this study, we examined the relationship between the iron regulatory hormone hepcidin and RLS. Hepcidin serves as a hormone that signals iron release from cells by interacting with ferroportin. We measured the expression and concentration of pro-hepcidin in the brain and cerebrospinal fluid of both RLS patients and control individuals. In CSF, we found that pro-hepcidin levels were significantly decreased in early-onset RLS patient samples, but not in late-onset RLS patients, when compared to controls. Conversely, in neuromelanin cells, substantia nigra, and putamen, the concentration of pro-hepcidin in RLS samples is significantly increased compared to controls. Functionally, hepcidin binds to ferroportin to limit iron movement from cells. Therefore, we provide immunocytochemical evidence that ferroportin is expressed by the epithelial cells of the choroid plexus and the ependymal cells lining the ventricles. These data suggest that sites of action for hepcidin include signaling the ventricular system for movement between brain and CSF. At this time, it cannot be determined if the lower levels of pro-hepcidin in the CSF represent a compensatory response to the decreased levels of iron in the brain or a defective signaling mechanism in RLS. Nonetheless, these data support the mounting evidence that there is a biological basis for RLS and the underlying mechanism involves iron management.


"if you can't explain it simply, you don't understand it well enough." Albert Einstein ;)


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