A complete RLS theory; oxalates and mast cells?

[XenMan]

Thanks to SnappK for providing the paper on mast cell activation syndrome. This makes it possible to put forward a complete theory on RLS due to oxalates. Using the anecdotal evidence of the low oxalate diet’s success with RLS, as well as numerous miscellaneous papers from other fields, a very good case can be presented for the cause and the symptoms of RLS that should apply as a basis for all; if not exactly in all cases.

For the basic myths, sleep deprivation without RLS has been shown to result in dopamine down regulation; a symptom not a cause of RLS. Brain glutamate increase has been seen in sleep deprivation without RLS; another symptom. Low brain iron has been seen from high oxalates, as shown in studies into autism; also not a cause of RLS but from the oxalates.

It could easily be connected that oxalate crystals cause mast cell inflammation and subsequent muscle and nerve tension. All the current successful treatments for RLS have an impact on muscle cells. These include the most successful such as dopamine, the electrolytes magnesium and potassium, iron, as well as exercise and physical treatments. As for all the other pharmaceuticals, they may impact the inflammation or the brains response to the nerve and muscle tension.

For most, the natural cycle of dopamine levels dropping at night would seem to then impact the muscles and nerve tension; making it worse.

That would make the symptoms the brain’s reaction to the nerve and muscle tension. As a physio told me, the brain produces maintenance pulses to keep track of muscles; especially when sleeping. With RLS it would appear that the brain then receives a signal back from the muscle it doesn’t expect, the muscle tension, and as a result produces the weird symptoms; most likely tactile hallucinations. You move your leg, a normal signal is sent from the muscle to the brain and the symptoms stop. This is why symptoms are often periodic; I counted to 45 between mine the other night.

The real speculation is where the genetic component is. It could be the inflammation or it could be alternatively, or include, the brains reaction to create symptoms.

If you put this all together and proved it, you would get a Nobel Prize in Medicine. Please mention me when you win it.

Post Thread:
http://bb.rls.org/viewtopic.php?f=5&t=9508&start=75
Mast Cell Activation Syndrome Paper:
https://jcsm.aasm.org/doi/10.5664/jcsm.8216
‘...RLS appears to be associated with MCAS.’ (Mast cell activation syndrome)

[badnights]

Nice work but some issues with it. As I mentioned in the other Topic, the mast cell study shows that WED/RLS is more common in people with MCAS (actually the result with females didn't reach statistical significance, but for sure, males with MCAS are more likely to have WED/RLS). Nothing is revealed in this study about whether people with WED/RLS are more likely to have mast cell activation syndrome, which I think is necessary for your theory to work.

I'm clear on what you mean by muscle tension, I think, but what do you mean by nerve tension?

I am interested in your physio's comment that "the brain produces maintenance pulses to keep track of muscles", especially during sleep". If you find more information on that, please share it. Thanks!

[XenMan]

I haven’t been able to find anything about ‘maintenance pulses’ through a medium level of searching. It must be a colloquialism used by physios with an actual term that is beyond me. I was going to ask in a forum but couldn’t find one that looked friendly. The timing of RLS symptoms intrigued me when they became a problem; like clockwork. I contacted a physio who does RLS research and in emails I mentioned this amongst other things she wasn’t interested in. She thought it sounded like these maintenance pulses. I got nothing else.

You can make claims this is a physical condition, or with an element, but there is nothing published other than studies on nerve irregularities of which there are a few inconclusive papers. The issue is always a lack of mechanism, instead we get and hear parroted the consistent vague claims like ‘it is from low dopamine’.

Assuming muscle tension and it is just inflammation in the muscles, why don’t steroidal anti-inflammatory drugs work? The mast cells look like a possibility for creating the muscle response seen with RLS, as well as an explanation for a mechanism of both cause and the ridiculous range of treatments that appear to impact symptoms. It is unlikely the MCAS is the only cause, but a cursory look at mast cells makes them the prime suspect to produce the environment for RLS through the musculature.

Oxalate crystals may be one source, but as so many things can go wrong with the body, as us older individuals know, a range of diets, environments and experiences could initiate mast cell issues. I can follow my path of 40 years of no RLS, and then the 12 year decline from inconvenience to absolute devastation. Antibiotics, diet change and now liberation, strongly linked to actions creating results. Just because there are many unknowns with RLS, there is not a rational freedom to say RLS causes are different in different people. You can't say that for diabetes, cancer, Parkinson's and other medical conditions; there is always a common mechanism.

It took me a while of experimentation, open to anyone to try and disprove, that the nerves are as much of a cause of RLS symptoms as the muscles. I found pressing the painful nerve areas, above and feeding the muscles, stop symptoms not only for the night but often successive ones. These spots are always along the bones of the calf, where I get my symptoms, and often inaccessible.

The RLS research focus currently is on brain neurology, which if right is good for all of us. But if it is wrong, it is wasted time and puts back a solution. Recently there was found to be a link to gingivitis and Parkinson’s, as well as glandular fever and MS. This highlights the wasted years looking in the wrong area based on dogma, with no real benefits for these conditions during this time.

RLS appears to be the same.

Thanks for your interest.

[Rustsmith]

XenMan, not all current research is focused on brain neurology although some of the biggest strides have come in this area. A year or two ago, Penn State published some work where they looked at venous blood flow in the legs. They found that RLS patients have higher flow under normal conditions but that following exercise that lead to hypoxic conditions, RLS patients did not experience the vascular dilation seen with non-RLS controls. They theorized that this could explain the increased severity of RLS in those who live at altitude.

There is currently a program at Stanford that is looking at SIBO and RLS. And another project at West Virginia Univ. was just published that looked at the use of yoga to improve RLS symptoms. I participated in a study at Ohio State that is looking at the use of foot massagers and heating pads on the legs to treat RLS.

And that doesn't touch on some of the studies currently being done that look at issues such as the increased incidence of depression and suicide in RLS patients.

So, there is a lot going on. The area that has the best potential for new treatments is the brain neurology work, but something could come from the other areas as well.

[XenMan]

XenMan, not all current research is focused on brain neurology...
...the best potential for new treatments is the brain neurology work

I should know better than to reply, but a few of your comments have raised my ire in the past so I'll bite.

The dominance of moderators across most forums are from sleep deprived, drug damaged (augmentation), and usually on a cocktail of pharmaceuticals documented to have major psychological sides. So the influence is towards the drugs as the answer, all in the brain and anything contrary is a lesser minority view.

It is a fact, if you target brain neurology with drugs there will be problems through side effects because it changes how your brain works, and the brain fights back to restore its norm. This is seen with all psychiatric drugs and for neurological disorders. The researchers and drug companies say there are no problems. But I know professionals who work in mental health and the drug use area, read the RLS forums and it is clear these are not drugs you would not take if you had a free choice.

I think you have to review your posts to see how strong your bias is towards neurological research, I have had discussions with you on this myself. Of course there is other research, you choose to misrepresent my statement. But these are often for commercial reasons or on the periphery of the much needed critical mechanism of RLS, that seems to constantly go wanting. You may be more optimistic than me, but academics are more about big pharma and the dollars, and 'publish or perish'. I follow science closely and there are some dreadful researchers publishing worthless rubbish; that someone then uses to build on.

I'm sorry, but research for yoga, foot massagers and heating pads are totally worthless; because you can try it out yourself. Do you need to have someone research if hot baths help?

At the end of the day we are both after a breakthrough in RLS, but just see the path differently. I sincerely hope you are right and I'm wrong, in that progress is in the right direction for everybody's sake.

Please don't turn this into the 'neurological debate'. If you disagree that is fine. But I'm sure there are some who want to step back, take a new view that may be completely wrong and then dismissed. Alternatively it may answer a lot of questions, ask some more, and in the off chance it is close to correct, worth pursuing.

[XenMan]

. Recently there was found to be a link to gingivitis and Parkinson’s,

Apologies to all, this was a mistake by me. It is in fact Alzheimer's disease. Very interesting if you have been following the utter frustration of research in this area. There are many parallels to RLS in that there was a focus on drugs to treating symptoms. An interesting read if you haven't heard of this.

https://www.newscientist.com/article/21 ... o-stop-it/

So floss and brush your teeth people.

I missed my opportunity to edit the post. Mods can change or leave it.

[Frunobulax]

XenMan, not all current research is focused on brain neurology...
...the best potential for new treatments is the brain neurology work

Please don't turn this into the 'neurological debate'. .

Occams razor is a sound principle. As many signs point towards some issue in the brain, it appears that research in that area is most likely to produce results. (Of course "most likely" implies that it's not a given.) We tend to see improvement only from drugs that pass the blood brain barrier like dopamine agonists, opioids or gabapentin. So a part in the RLS mechanism is most likely in the brain.

Of course, the brain is no isolated system. PD is down by 50% in patients where the vagus nerve was cut https://neurosciencenews.com/parkinsons ... logy-2150/, and scientists have verified that WGA (a lectin contained in wheat) travels from the gut to the brain via the vagus nerve in mice. Why shouldn't there be a similar mechanism for oxalates?

Personally, I think that inflammation in the brain may very well be the reason for RLS (or maybe one reason out of several possibilities). We have linked inflammation to many neurological diseases. Virtually all antiinflammatory drugs don't cross the blood brain barrier, so they wouldn't affect RLS if this is true. RLS is much more likely if our antioxidants are down, that can clear the results of inflammation (oxidative stress), as evidenced for example by https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5886433/. Oxalates are linked to high uric acid, which promotes systemic inflammation and depletes us of the antioxidants. Oxalates could very well raise inflammation in the brain, in that Alzheimer article you linked the key issue seems to be inflammation too, caused by gingivalis. This is all consistent with the fact that only some RLS sufferers profit from low oxalate diet, of course there are plenty other ways to promote inflammation.

I wouldn't expect antioxidants to help a lot with RLS though. Low antioxidants could be compared to scars: If you treat scars you won't help with the damage from the wounds that left those scars. In our world, inflammation means the immune system is chronically activated which includes toxic warfare with free radicals. Even if they are cleared up by antioxidants later, they will have done their damage.

[XenMan]

As many signs point towards some issue in the brain, it appears that research in that area is most likely to produce results...

Seriously??

Two people have expressed this and no one else has commented or challenged.

This is a serious wakeup call to anyone who battles with RLS. As I have said, I hope I’m wrong for all your sakes; as I'm all good now from reducing oxalate levels. But for your future success there should at least be a consideration to put all biases and assumed knowledge behind for just a moment of clarity. Ask yourself what is at stake if a course for a cure or treatment has already been decided for a mostly unknown condition?

The papers on dopamine downregulation and elevated glutamate in RLS ignores to mention this occurs from sleep deprivation without RLS. If drugs to target these symptoms worked well there would be no forums or need for further research, as a satisfactory solution would have been found. But still there seems to be a consensus that we need more neurological drugs with unknown long term consequences.

This tunnel vision of a cure/treatment before properly understanding a condition is seen nowhere else, or results in negative outcomes. Usually you find the mechanism first to prevent or treat, with other measures for symptoms if not completely successful. I presented the theory of a model, and even based on that being hypothetically correct, there is still a dedicated view for only using neurological pharmaceuticals.

This is doing my head in, so it is time for me take another extended break from the madness.

[stjohnh]

...
This tunnel vision of a cure/treatment before properly understanding a condition is seen nowhere else, or results in negative outcomes. Usually you find the mechanism first to prevent or treat, with other measures for symptoms if not completely successful...

That's actually not true. Most illnesses that have treatments available were treatable before the mechanism of the illness was found. Examples include penicillin for pneumonia, streptomycin for TB, most cancer drugs, digoxin for congestive heart failure, meds for high blood pressure, prednisone for lupus, morphine for pain, etc. etc. These illnesses had effective treatments available before the physiologic basis for the illnesses was discovered.

There are actually only a few illnesses in which the pathogenesis was worked out before effective treatments became available. It IS true that knowing the mechanism of an illness has spurred development of additional treatments besides the ones discovered more-or-less hit or miss. For example, high blood pressure NOW has more effective treatments with fewer side effects than 40 years ago, in large part due to better understanding of the mechanisms of high blood pressure, but it was still treatable 40 years ago.

[Frunobulax]

But still there seems to be a consensus that we need more neurological drugs with unknown long term consequences.

And here you show exactly the bias that we allegedly have. I have never, ever called for more neurological drugs, and I spent most of my time during the last years to research how I can treat my diseases without adding more drugs (even though I will consider drugs if necessary).

The issue with drugs is more complicated. Most of our drugs will force our body to do something different instead of trying to fix the issue.
One example: If a doctor prescribes dopamine agonists, he assumes that our body produces not enough dopamine so we force it into our system. I think this is wrong in most cases (i.e. non PD), because the dopamine levels in RLS patients tend to be normal. It may fix the symptoms for a while, but it won't cure the patient and it will most likely lead to more damage in the long run.

My approach, which may or may not be defined as functional medicine, is to find out *what* is wrong and how we can fix it with minimal side effects, via diet and environmental changes if possible, via drugs if necessary. The iron approach is fine for me (even though it seems to work for only half of the patients), for various reasons we have issues with our iron metabolism and may have iron shortage in the brain, and supplementing iron fixes this.
But I happen to believe that the issue is in the brain nevertheless, and we must do changes that affect our hormone/nutrient/toxin metabolism in the brain.

[badnights]

I support neurological research but I don't want to see more pharmaceuticals. I want to understand what is wrong so I can fix it.

I think we all want research into the causes of WED/RLS in order to cure ourselves of it, or at least improve our lives. It would be best if we could do that without pharmaceuticals, and I doubt if anyone here is going to argue with that.

We can't know what to do to fix ourselves if we don't understand what is wrong. The research is to find out what is wrong. The evidence that points to central nervous system dysfunction in WED/RLS is varied and strong, so the brain and the rest of the CNS have become a topic of research. There are also intriguing hints that other systems are involved (hypoxia in muscles, peripheral nerve dysfunction, complex interactions between the gut and the CNS, varicose veins, I know I've forgetten some), so there is a bit of research in those areas, especially peripheral hypoxia. As evidence gathers for the role of these other systems, the amount of research in those areas will increase. We need it all. We need research into all the systems that might be involved.

You're right that the collective focus of WED/RLS research is too heavily on pharmaceuticals. It is a big problem that pharmaceutical companies provide so much of the total funding available for research. At least the grants that the Foundation provides for research are not from pharma companies. But the amounts are so little compared to what is needed.

I agree that we need more holistic research, looking at multiple body systems and studying especially how diet and gut health affects disease states. It's incredibly complicated to study properly, and complicated means expensive, so a puny 20,000-dollar grant won't end up being used on that kind of research.