Solving RLS: Largest Genetic Study to Date may help - Medscape article

[amrob123]

Medscape article

medscape.com/viewarticle/so...

[ChrisColumbus]

Interview with Steven Bell:

thenakedscientists.com/arti...

[amrob123 in reply to ChrisColumbus]

Thanks ChrisColumbus. That interview rounds out the Medscape article nicely.

[DesertOasis]

Hi Amrob, my takeaway from the article is I will no longer be using the word “genetic” when referring to our lousy dopamine receptors. We cry (me included) about lack of RLS research, yet at least in terms of analyzing possible genetic variables and mutations, there seems to have been quite a lot done in this area over the last two decades.

Variations in the DRD2/DRD3 gene(s) is what will lead to lousy D2/D3 receptors and we with RLS just don’t seem to have any defects there. These genes were specifically analyzed and the researchers clearly came up empty handed, in terms of RLS. So for now I’m dropping the word “genetic” from my RLS lexicon

There’s a vicious circle going on with us RLSers and it’s impossible to say which component part came first. It seems that via nurture (and possibly a genetic predisposition) we may have first had lousy D2 receptors, which led to excess dopamine, which then led to low brain ferritin, possibly? Dopamine and iron can have a toxic relationship and harm the brain so our low ferritin MAY be a bodily defense mechanism to that excess dopamine? And researchers have found that DAs will increase brain ferritin, or as they put it “attenuate spinal cord iron deficiency. “ I’m guessing this attenuation happened because the DAs reduced that large pool of extracellular dopamine, thus allowing for more of that potentially toxic iron to hang around? pubmed.ncbi.nlm.nih.gov/210...

On the other hand, if it all started with low brain ferritin, then that may have been the first step which eventually led to our lousy D2/D3 receptors, which then led to excess dopamine and the inability to clear our brains of that increased extracellular dopamine which then in turn insures our brain ferritin remains low. A vicious circle no matter how you look at it, or which came first.

RLS experts have tried every which way to increase our brain ferritin, with very little success. Yet, have you ever heard of them trying to increase the number and density of our dopamine receptors? No, right? Then WE need to try, so I think. All of us on here! The whole world is trying to discover ways to up-regulate dopamine receptors if for no other reason then who doesn’t want bigger, better dopamine rushes? We can learn from these people and not wait for the so-called RLS experts.

Well, I finally took my own advise and I have been religiously taking berberine for over two months now. I felt zero improvement for 60 days, possibly due to use of a PPI in the beginning. I’m a good subject for this experiment because I tend not to take my treatment of choice (iron) until I feel the RLS kick in, which is always right around midnight, give or take 15 minutes. This past week I’ve waited till 1:30am and still no RLS. Then I take the iron and go to bed. The strange thing is, within about 5 minutes of taking the iron, the RLS kicks in - mildly - and goes away in 15 to 30 minutes.

I must have the world’s strongest gastrointestinal biological clock. Any tiny amount of food after 10pm causes not only near immediate RLS, but cramping quite often as well. Hell hath no fury like an awakened GI tract. Not sure why food (any food) also trips my RLS clock? But the RLS and cramps are of short duration after I do this so it’s worth it in the name of science.

One person with one week of RLS relief does not a clinical trial make. If it continues on for another few months I will post about it and if it does continue I will give up the iron. The reason I’ve been trying berberine is because there are several articles indicating that it increases the number and density of D2 receptors and it’s also supposed to lower blood sugar and cholesterol and it’s a secret ancient Chinese herb to help cure whatever ails you - especially parasites 🤤

My big point is - rather than waiting for the RLS medical community to discover some faulty gene and then possibly find better treatments based on that faulty gene, I hope people with RLS try to up-regulate their receptors with safe and natural therapies. I read recently that sun exposure will enhance our dopamine receptors 😃🌈💥🦋💯 researchgate.net/publicatio...

[amrob123 in reply to DesertOasis]

Thanks for sharing the early results of your berberine trial. I have been minded to try it (am currently re-trying dipyridamole) and so look forward to hearing whether your good results are sustained. If i recall correctly you tried berberine previously (was it you who posted some pictures of different coloured liquids)? What made you stop it the last time?

Do please keep us updated on your experiment.

[DesertOasis in reply to amrob123]

Life is strange, sometimes for the better. I worked out late - till 10pm. Ate dinner at 10:30pm, despite my better angels, and right now at 12:45am, I’m sitting here with zero RLS. Do I take iron?

[Rayme in reply to DesertOasis]

I've often gone round in circles trying to figure out what's going on with RL (iron, dopamine, glutamate, other). I'd really like to hear how it goes with berberine. I imagine it would be erratic before you see any constant improvement, it could take a very long time. I hope it works!!! I took berberine for a week but was unsure whether to continue due to already having low blood pressure and not confident to keep going at that point especially as the RL did seem a bit worse. Or was that my imagination! On another point - sunlight. I once had a very slow relaxing interesting day out walking through a cavernous riverbed and looking up at the walls and to the light, so beautiful. That night I had zero restless legs, unheard of as I have a severe retractable rls. 😊

[DesertOasis in reply to Rayme]

Yes! Your RLS should have been worse if you took the berberine toward the evening. That’s how you know it’s working. Even during the day your legs may act up about 30 minutes after taking it and for a few hours. Never take Berberine at night. Did you try a bioavailable kind? Berberine, in general, is highly unbioavailable. Maybe 4% gets absorbed into the bloodstream and the rest heads straight for the large intestine. And maybe that’s how it works - via the gut microbiome. I believe berberine was looked at in terms of PD, and yes, because of its effect on the gut. I might be making that up?

RLS is somewhat more complicated then how I explain it above. There’s a whole cascade of other events (and chemicals) that happen in the process of getting that pool of dopamine into a neurotransmitter form that bounces its way down the spinal cord and to the peripheral nervous system. And I know there’s this whole Yin/Yang thing going on between the D1 and D2 receptors.

Taking berberine is kind of a personal decision. I doubt any doctor would give his blessing, maybe a chiropractor? Sunshine and magnesium would more likely get your doctor’s approval.

Isn’t it amazing that a day of sunshine made a nice difference in your RLS? You must give that another go. A small part of me is amazed each and every time the ferrous bisglycinate relieves my RLS and that of others on here. It’s actually earth shattering as far as RLS goes, so I think. And it wasn’t my idea, I read about it on the internet. It was only about three years ago that I was having a debate with Manerva (another member on here) whether such a thing is even possible. I totally understood where he was coming from. If you only think in terms of serum ferritin, then yes, the iron at night trick seems to defy gravity. He wasn’t going to let it go till Sher78 and I admitted the possibility that it was all placebo. Over three years for Sher (and 10 for me) I don’t think it’s placebo 😅

There’s so many dopamine antagonists out there - Benedryl, Tagamet, SSRIs, Melatonin, HRT - but they’re not viable treatments to up-regulate our receptors because, first off, they’re not exactly “benign” the way sunshine, anaerobic exercise, magnesium, intermittent fasting and hopefully berberine is. Plus, some of those drugs have long half lives so they will definitely make your RLS worse at night, unlike Berberine, which has a short half life.

I’m not expecting the berberine to be erratic. And I’m only hoping that it scales up my receptors to the point they were at in my early to mid-forties when RLS was not an every night thing and I didn’t need the iron except when I did something stupid like took a Benedryl or Tagamet or Melatonin before bed. I’m practically there now. Unlike magnesium, I don’t believe berberine is something that should be taken every night, non-stop. Another member on here, RKM7, took it for three months and I advised her to take at least a month break and see how long the effects last. Then she can always start up again which I assume would always be necessary because our receptors always crawl back to baseline when they’ve been up or down regulated via substances, be it berberine or a DA or even intermittent fasting. If you stop any of these things long enough you will be back to square one.

Phew! Long post.

[DesertOasis in reply to DesertOasis]

Some evidentiary support for berberine:

onlinelibrary.wiley.com/doi...

tandfonline.com/doi/full/10... - this is a wow. Yet despite all these fab claims I have not seen improvement in my IC or sub-clinical CFS. I was not expecting to, just RLS.

sciencedirect.com/science/a....

[Rayme in reply to DesertOasis]

yes, interesting articles...and I think doing intermittant berberine is do-able for me. I still have plenty in stock to use! Thanks for the info.

[DesertOasis in reply to Rayme]

Go for it! Then keep us posted. 😁

[Sausewind in reply to DesertOasis]

Sounds interesting. And I heard vitamin d is important. I try a the moment padma 28, its an tibetan recipe of approx. 20 different herbs. I try all before taking meds.

[amrob123 in reply to Sausewind]

A very good idea to try non-medication options first Sausewind👍

[DesertOasis in reply to Sausewind]

Ouuu, Padma, sounds interesting. Have to check out what those herbs are.

[Sausewind in reply to DesertOasis]

padma.ch/en/products/padma-...

[DesertOasis in reply to Sausewind]

Thank you!

[Sausewind in reply to DesertOasis]

nidrarls.com/Sounds interesting, available in US first