Cause or contribution factor to RLS

I say "just the restlessness". It's quite horrible, night after night, you want to jump in the river to end it all, I don't mean to sound like it's insignificant.

How are you and what are you taking for your RLS these days?  I miss our RLS side chats.  Interesting about the liver having a circadian rhythm.  Actually quite fascinating.  Maybe our unbound blood iron levels drop at night because our liver is doing a little housekeeping?  Iron, once bound up, is relatively harmless, but the unbound iron is seen as a troublemaker by our liver?

Hi Udon, how are you?

Of course there's maybe two sides to the dopamine problem, pre-synaptic and post-synaptic. Since the only thing that really works for me is a dopamine agonist (I now keep needing 3x2mg of ropinirole to get through the evening and night), I think my problem is mostly post-synaptic. What regulates the number of post-synaptic dopamine receptors, and what determines how active they are? It would also be good know just how dopamine interacts with movement control too.

I read somewhere that dopamine is released in a flash when we go from sitting or laying to standing.  Dopamine as a neurotransmitter is what balances us when we stand and coordinates movement when we walk.  And that is why RLS abates when we stand and walk - because dopamine is released and I believe the more "imbalance" the brain senses the more dopamine that is released.  I once tried leaning while watching a movie because I had RLS and it helped a little but did not completely eradicate the RLS the way regular standing and walking does.  Strange feeling to have RLS while standing and leaning.

In my old age I find that the RLS is triggered most every night.  And the iron still provides relief however I have begun using an iron patch more and more because many nights my stomach is not empty when the RLS strikes.  The patch is 45mg of the iron bisglycinate and I prefer the 25mg capsule, but such is life.  I pretty much know for a fact that in my case late night snacking will make my RLS worse than it has to be - much the way antihistamines or antacids do.  The only thing I can surmise is that the serotonin that is released from eating competes with what little dopamine is being transmitted by my puny d2 receptors at night and ultimately leaves me with RLS.  Even a large meal earlier in the evening where I get done around 9pm will leave me with RLS around 9:30pm whereas normally it does not kick in much before midnight.  Like antihistamines I find that the food induced RLS will subside somewhat after a few hours.  Supposedly our guts have a circadian rhythm and like our pre-historic ancestors we should consume most if not all of our calories between sun-up and sundown.  As with all other substances, late night eating is not the cause of my genetic RLS but can trigger it or make it worse than it has to be.

Yes, it has begun to dawn on me that there is nothing slow about dopamine neuron transmission. I'm not so sure about how fast D2 receptors can be created or destroyed and rather ignorant of how triggers for it work, and, of course, then there's the problem of what controls the amount to which they work.

I can control my RLS quite significantly with night-time binges – I'm talking about a couple of big bowls of porridge oats with whey powder and/or fruit juice plus maybe some bread and/or fresh fruit. If I just take a ropinirole in the afternoon and then one just before bed, such a binge at one or two o'clock in the morning will get me through the night usually. The trouble is my weight and waistline would just keep going up and up, which, at the moment, I tend to think may be less healthy than an extra ropinirole.

If I don't take a ropinirole during the afternoon, by evening my RLS may be so severe that even when I stand up and walk round the room a little, it can still hit me almost as hard as if I've been given a punch or kick in the back of the knee. On top of that my torso is also driving me crazy twisting and twitching about.

It sounds like you've given up on the iron or it has given up on you.

Well, I don't think it's the most likely problem in my case.

The way I'm currently looking at it is that for RLS problems to occur there isn't enough dopamine coming through postsynaptically. This may be a problem with dopamine production which is probably in most cases because of a lack of iron or because of a lack of control mostly relating to processes which involve iron. On the other hand it may be a problem with the postsynaptic D2 receptors, there not being enough of them, or their not letting enough dopamine through. Since studies show normal levels of dopamine in RLS sufferers, those presumably with no iron problem, I think one has to look at the postsynaptic situation.

Just today, I was reading that ropinirole above 1 mg might well indicate augmentation, and that augmentation is not a worsening of the underlying RLS problem, but a sort of rejecting reaction of the postsynaptic D2 receptors to the continued use of the agonist. It's thought that opiates are better in this respect. A lot of RLS sufferers tend to switch occasionally between the two treatments, I read. Opiates stil act on the D2 receptor though, I also read.

Hmm, on the bright side the iron seemed to provide relief for you for a month or two.  Nothing good lasts forever.

I think though that when I tried other things there was an improvement also, and I wonder that it is not the result of the hopeful mindset one gets into which dopamine sees to reward.

Why did u stop? Did the placebo effect wear off? As I recall your daytime dose provided complete relief until evening time. Were you expecting a cure? Sadly, iron is not a cure just one of the better more natural RLS relievers. But you know that from first hand experience.

I still take 56mg of iron in the evening. 180mg is an awful lot, and I think my dopamine had got wind of the fact that it wasn't something it believed real! – It wasn't really working for me anymore. I've had as much success forcing myself into positive realistic thoughts rather than fantasizing and daydreaming, though I'm not at all sure why the latter shouldn't be healthy when one wants (and needs) to relax.

Life as I know it would cease to exist without the iron bisglycinate.  Iron is to my anemic RLS brain what insulin is to a diabetic.  Not a cure but nevertheless necessary.  Right now I'm doing a protocol for another benign condition but my goal is to take 500mg of berberine (a dopamine Antagonist) by day in hopes that it will build up my lousy dopamine receptors.  I think of iron as fuel or even glue for our d2 receptors at night so that dopamine will stick to the receptors and in turn be transmitted to CNS.  But I don't think of iron as "building up" the receptors.  Supposedly intermittent fasting and some other substances that are dopamine antagonists will actually increase the number and density of the receptors - at least in rats - and its not just the RLS dopamine receptors that need some beefing up - it's also those of Parkinson patients and drug addicts.  Probably starting in September I will give the berberine a shot for three months.  Long story short, just the way that dopamine agonists down-regulate the receptors, dopamine antagonists should up-regulate them, right? 

There are differences between the iron content of the RLS brain and the non-RLS brain. We really need to know what's going on, detail about the neuronal circuits, what brain activity triggers what.

A number of anti-psychotic drugs are dopamine antagonists and I seem to remember some medical papers on those and RLS. An agonist should increase the activity of a receptor and an antagonist decrease it, I believe.

In Parkinson's (PD) the neuron doesn't exist, of course. I've been wondering lately if there's anything to be made from the difference in motor control between PD and RLS. Does the lack of motor control in PD come with any sort of discomfort (other than not being able to what you otherwise might)? PD sufferers can respond to emergency stimulation, I read. Maybe that's a bit like doing something stimulating or active when one has RLS: in one case presumably sending stronger signals through neurons one has left, and in the other getting the neurons to fire and receive across the synapse effectively. Whatever, it occurs to me that a few hundred thousand dopamine neurons is not that many compared with a whole nervous system, and we need to know the best way of looking after them.