I have recently had great success mitigating my RLS. Rather than continue to wander blindly not knowing why I had RLS, I did a test to see which of my neurotransmitters were off. I specifically did this one from ZRT Laboratory: zrtlab.com/test-specialties.... What I found out is that I have low Dopamine, which of course goes with RLS, but I also had extremely high Histamine. Histamine is an excitatory neurotransmitter and so it up regulates and aggravates all other imbalances. It was also keeping me awake at night. I worked to get this under control by following a strict Histamine Intolerance diet and taking DAO with meals. What I found is that my whole system calmed down and my RLS dropped to 5% of it's original intensity. It became enough that if it woke me up at night I could get back to sleep taking some Relora, which controls cortisol with magnolia bark and another herb, and some Valerian, which helps convert Glutamate back into GABA so that you can sleep. So long story short, get your neurotransmitters tested to really find out what your problem is rather than blindly taking drugs that may or may not be targeting your actual problem. I'm not saying high Histamine is your problem, but if you find out what your complete Neurotransmitter profile looks like you can work with a qualified Naturopath to balance your entire system and greatly reduce your problem. If you don't have a Naturopath I believe that ZRT Laboratory might be able to help you find one.
Test your Neurotransmitters to get to... - Restless Legs Syn...
Test your Neurotransmitters to get to the bottom of your RLS
I have to add that I also am taking supplements to manage my Dopamine levels. I take L-Tyrosine, Gingko Biloba, Magnesium, and Berberine daily. I found this to be a helpful article for raising Dopamine levels naturally: healthline.com/nutrition/do..., but these supplements were also recommended by my Naturopath. My Naturopath also monitors my Iron levels, since that plays a part in RLS. Additionally I have been using natural hormone replacement therapy since there is a huge relationship between menopause and the onset of RLS: pubmed.ncbi.nlm.nih.gov/187.... So again work with a Naturopath, test your Neurotransmitters and hormones if necessary, and address your whole health picture to manage your RLS. That has worked for me!
I'm with you on using natural supplements to raise those neurotransmitters. I have found that Gaba is one of the most important for me, so I use Gaba as an amino acid to help with RLS as well as sleep. Also, myself being upper sixties, and RLS having come on with menopause (tho I had very mild RLS as a child and a few other times thru my life,) I have found that balancing those hormones is VERY IMPORTANT. I did have some testing a few yrs ago at ZRT, but it would get a bit expensive to test frequently. So maybe again later. However, what I have found over and over is that I myself respond very well to small amounts of DHEA and to bioidentical progesterone cream. If I do not take DHEA, then nothing else helps at all. This is not only pertaining to RLS, but to sleep. If I take Dhea, then I can sleep quite well. If I do not take it, not only can I not sleep, or sleep very fitfully with RLS starting up, but anything else like 5 HTP, melatonin, valerian, glycine, taurine and yes, even GABA by itself, do not make any difference. So, I am sticking with small amounts of DHEA - one of the hormones that goes down drastically as one ages, till there is only a very small percentage being produced by age 70/80.
Actually, I do not usually mention DHEA on this site, as there are perhaps a lot of younger people who should not be using it as their bodies are still producing enough of it. I do not want them to get the wrong idea. But then, there are a lot of older people on here who might benefit. So, I am mentioning it now. HOWEVER, people should do their own homework and not take something just because someone else is. There is information out there, doctors who can help (depending .)
Thanks for bringing up the subject of menopause/hormones. And not leaving men out - men have hormones too, and they decrease as the man ages. So they should look into this subject also.
It's interesting that you mention DHEA because I have been using a bit of it as I go through menopause to stop night sweats and it works very quickly. But like you said, young people shouldn't use it.
It is a complex issue--RLS, and I think for different people different things or different amounts work better or not at all. Also, as one ages it seems to change a bit as well. Tho that is how it is for all sorts of bodily issues as we age and hormone levels change. Dhea is a big one for me, tho I take small amounts. It is the number 1 thing for me, for those hot flashes. I used to get them terribly. Dhea under the tongue can stop them in minutes.
I absolutely agree with you. RLS is very complicated presumably because it seems to be an issue of the HPA Axis which governs so many bodily functions.
DAO lowers or blocks histamine in the gut, but B12 lowers it elsewhere:
jstage.jst.go.jp/article/bb...
HNMT (Histamine-N-methyltransferase) is the enzyme that needs B12, folate and methionine) to break down histamine in the tissues.
ncbi.nlm.nih.gov/pmc/articl...
So for whatever reason, DAO stops the histamine that triggers by RLS. I've found some papers that link mast cell activation syndrome with RLS: ncbi.nlm.nih.gov/pmc/articl.... During the night when my RLS acts up I take 4 DAO pills. If that doesn't stop the twitching I take 4 more and within 3-5 minutes it stops. I'm an asthmatic and definitely have high histamine issues so presumably histamine is the gasoline that starts my RLS on fire, and DAO puts that fire out for me within minutes. It's an expensive fix because DAO pills are about $1 each, but it has been worth it to be able to stop the twitching and go back to sleep.
Thanks for sharing this.
Very interesting that you were able to get a test for your neurotransmitter levels. I don't think that it was normally possible to directly measure neurotransmitter levels in the brain.
What samples were taken?
Since histamine is also involved in inflammatory responses then high levels of histamine might indicate the presence of inflammation, possibly an allergy.
Inflammation IS a mediating factor in RLS and can make it worse.
Anti histamines conversely can also make RLS worse, especially sedating ones, as they lower dopamine levels.
RLS is not due to low dopamine levels. It is due to a lack of D2 dopamine receptor sites. This means that even if dopamine levels are high there is still a dopamine dysfunction. Dopamine levels in RLS are often high, not low.
Hence, I wouldn't really recommend anything which raises dopamine levels. The end result of raising dopamine levels can be augmentation.
All the things you're trying for your RLS makes it diffcult to decide which ones are working and which aren't.
If they work for you and you're happy to continue taking them ALL that's great!
I would say however.that you don't seem.to be taking the main supplement that is most likely to treat your RLS and that is iron.
I wonder.how your Naturopath.is monitoring your iron.
Standard blood tests for iron deficiency for people with RLS are serum.iron, transferrin, transferrin saturation and ferritin.
If all others are normal, the ferritin is most significant. The guidance is that if ferritin is less than 75 then you should take an oral iron supplement.
If it's more than that, but less than 200, it's really only feasible to increase it by having an IV iron infusion. Idealky, it should be at least 200.
Iron therapy is a treatment for RLS as iron deficiency is the main causative factor in RLS lesding to dysfunctions in adenosine, dopamine and glutamate.
I'm sceptical of any test for neurotransmitter chemicals thats not extremely invasive.
Yes I'm also sceptical.
If you go to the ZRT web site apparently it's a urine test.
zrtlab.com/test-specialties...
The explanation they give does seem a bit dubious. There's no reference to any scientific basis.
I don't find it easy to follow their explanation, but it does seem that assuming the tests are valid, they are measuring total neurotranmitter levels, not levels in any particular part of the brain., or even particuilar part of the body generally. So, for example, what does it mean if dopamine levels are low?
Furthermore some of the "neurotransmitters" are also hormones e.g. epinephrine (UK adrenaline) and norepinephrine (UK noradrenaline). It doesn't appear as if the tests differentiate between adrenaline the neurotranmitter and adrenaline the hormone.
The other rather dubious implications which arise form statments that a lack of specific neurotransmitters is "associated" with specific mental health problems.
This is true, but it's not really possible to say that the mental health problem is caused by the lack or the other way round, the lack is caused by the mental health problem.
So for example, depression is often caused by specific events, a berevament, divorce, lockdown etc. Not a sudden biochemical imbalance. Correcting the imbalance artificially (however that's done) might mask the symptoms, but doesn't deal with the cause.
Ultimately whether such tests can lead to a diagnosis of RLS or to the identifcation of a cause of RLS is not at all obvious. E.g if dopamine levels are low, does that mean you have RLS?
Conversely if you DO have RLS and dopamine levels are low for example, what does that mean.? RLS is not due to low dopamine levels!
Furthermore although neurotransmitter dysfunctions lead to the symptoms of RLS, you have to ask, what causes the dysfunctions.? The main cause, therefore more fundamental cause is brain iron deficiency.
Iron therapy is established as a treatment for RLS, not just symptomatic relief.
A more direct test fo brain neuortranmitters, I guess, would have to be a test of cerebrospinal fluid requiring an invasive procedure.
Manerva, you are correct (as usual 
)... the dopamine level is HIGH in RLS because of not enough D2 receptors. I remember the discussion on here about augmenting because dopamine agonist drugs can create new receptor sites thereby requiring the body to have more and more of the dopamine drug to relief symptoms. ( there is actually a D4 receptor now discovered by a Dr. Ferre that may be a better target for dopamine drug development... this was published in the RLS foundation blog in 2018)Conversely, RLS people usually have low levels of receptors of adenosine which is the chemical in the brain that regulates neurochemicals and this leads to abnormally high levels of glutamate and dopamine as well. Research says this may be the underlying cause of both PLMS and hyperarousal in RLS. In summary, I find EBurgh1968's information very interesting, especially since I have suffered from histamine like symptoms nearly my whole life. I can only say that diet and cutting down/out alcohol has helped most of my symptoms but I do know that histamines from a medical perspective can and do cause inflammation of the CNS and digestive tract.
I agree, another theory, I believe, is that the dopamine agonists as well as downregulating D2 receptor sites also upregulate D1 receptor sites which take away the dopamine from the D2 sites.
Now there's a D4 site too?
Yes, I've also read about adenosine and trials with dipyridamole to correct adenosine levels.
Certainly, it would seem that if histamine excess or a histamine intolerance is an issue in some people then DAO may be a solution to prevent histamine being absorbed but the other enzyme that acts inside the body, histamine-N-methyltransferase, might also be helpful. I don't know if that can be ingested as a food supplement or not.
ZRT Labs test is definitely a urine test, but it got to the bottom of the problem for me. Histamine is definitely the gasoline that lights the fire of my RLS. Additionally my dopamine levels showed up as being low on this test. While the urine test doesn't show exact neurotransmitter levels in the brain, it is an indicator of neurotransmitter levels and that information has helped me to manage my RLS. I've found some papers that link mast cell activation syndrome with RLS: ncbi.nlm.nih.gov/pmc/articl.... During the night when my RLS acts up I take 4 DAO pills. If that doesn't stop the twitching I take 4 more and within 3-5 minutes it stops. I'm an asthmatic and definitely have high histamine issues so presumably histamine is the gasoline that starts my RLS on fire, and DAO puts that fire out for me within minutes. It's an expensive fix because DAO pills are about $1 each, but it has been worth it to be able to stop the twitching and go back to sleep. As I continue to research the link between mast cell activation, histamine intolerance, and RLS I am finding more and more NIH papers. I find it interesting that traditional antihistamines like Benadryl for instance, actually aggravate RLS. It is my belief that this is because Benadryl doesn't get rid of excess histamine, but rather blocks your body's symptoms from the excess histamine. So the histamine keeps building up internally and aggravating the RLS while you do not appear to have any allergic symptoms. I have to chemically breakdown the histamine out of my body with DAO to relieve my RLS symptoms.
Could you explain what is DAO please?
Diamine oxidase (DAO) is an enzyme that helps break down excess histamine in your body. healthline.com/nutrition/da...
Thanks for the link.
Interesting.
I think it worth exploring this further.
The first question is that this article writes about histamine intolerance and this may not be the same thing as excess histamine.
It doesn't make clear if the problems it identifies are due to just intolerance or excess or both
Perhaps obviously a remedy for both would be to reduce histamine levels.
In the case of an excess, the question is what the excess is due to.
If it's due to excess in the diet then this can be remedied by avoiding histamine rich foods. If it's due to this and/or lack of DAO then it can be remedied by taking a DAO supplement.
However, this will not reduce levels of histamine already in or manufactured within the body.
If the problem is simply an intolerance then it's difficult to say how much you need to reduce histamine levels. SOME histamine is essential for normal processes.
This is a different scenario to say gluten intolerance whether this is celiac's disease or non celiacs gluten sensitivity. In this case you'd aim to elminate gluten entirely and this is possible.
DAO may work in some cases but it's not going to be a catch all remedy.
I am guessing that it works for people who have RLS connected to mast cell activation syndrome, and that is definitely me. Histamine is the gasoline for my RLS, but glutamate might be the gasoline for other people's RLS. That would be something each person needs to uncover on their own.
Yes great reply.... I totally agree with this! I think histamine levels must play a role which also explains why certain high histamine foods can Also aggravate restless legs. Thanks so much !!
That definitely was the case for me. I've found some papers that link mast cell activation syndrome with RLS: ncbi.nlm.nih.gov/pmc/articl.... During the night when my RLS acts up I take 4 DAO pills. If that doesn't stop the twitching I take 4 more and within 3-5 minutes it stops. I'm an asthmatic and definitely have high histamine issues so presumably histamine is the gasoline that starts my RLS on fire, and DAO puts that fire out for me within minutes. It's an expensive fix because DAO pills are about $1 each, but it has been worth it to be able to stop the twitching and go back to sleep.
Also for anyone interested, here’s a histamine intolerance diet pdf:
histaminintoleranz.ch/downl...
Thanks but I couldn't access the site
This link below works, but I couldn't identify what link to follow after that.
However a couple of useful excerpts are -
"Histamine is a substance, which is naturally produced in the body and regulates various functions (mediator, messenger, transmitter). In case of infections and allergic reactions, histamine puts the body's defense mechanisms on the alert. Histamine is also an inflammation mediator, a tissue hormone and neurotransmitter; it plays a role in the circadian rhythm, the bowel movements and many other processes. The body may produce histamine, store it in certain cell types and if necessary release it all at once."
and
" If the amount of histamine in the body is - for whatever reason - too high for the body to eliminate, the histamine level increases too much. Food is usually the main source of histamine, and insufficient enzyme activity of diamine oxidase (DAO) and/or histamine-N-methyltransferase (HNMT) are the causes of an imbalance between the histamine intake/release and degradation."
I think you have done well to work with a Naturopath Clinician. Rather than order testing yourself and then make choices on supplementation. The key is coordinating test results with observed and chronicled health problems. It is indeed controversial - panned by Dr. Weil, and others. But espoused by many - again, with the caveat to work with a clinician to interpret results and treatments. Here is a scientific paper with discussions...
knowbalance.com/storage/app...
My Naturopath Clinician has been invaluable in helping me to get to the bottom of my RLS. I am also a Chemist and so we have worked together to find a strategy to help relieve my symptoms, and as I have mentioned above the DAO stops the RLS during the night within a few minutes. I am thankful that my Naturopath is willing to partner with me to unlock the particulars about my health.
When I go onto their website I can only log on if I am testing lab. The site then refers me to local testing labs in my country. Were you able to obtain a test directly from ZRT lab?
Great information...thank you.
I went through my Naturopath.
I want to add that in the past year I have found a better way than Relora to shut down my RLS at night. I've found some papers that link mast cell activation syndrome with RLS: ncbi.nlm.nih.gov/pmc/articl.... During the night when my RLS acts up I take 4 DAO pills. If that doesn't stop the twitching I take 4 more and within 3-5 minutes it stops. I'm an asthmatic and definitely have high histamine issues so presumably histamine is the gasoline that starts my RLS on fire, and DAO puts that fire out for me within minutes. It's an expensive fix because DAO pills are about $1 each, but it has been worth it to be able to stop the twitching and go back to sleep. I realize that HNMT should in theory be what shuts down histamine levels outside of the gut, but for whatever reason DAO works within minutes for me.
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