Quotes from 2 Legendary RLS Researchers connecting RLS to Inflammation

[CalmLegsJL]

In 2011 Doctors Leonard Weinstock, Arthur Walters and Paisit Paueksakon published a scientific paper called "Restless Legs Syndrome: Theoretical Roles of Inflammatory and Immune Mechanisms."

This was a breakthrough study that discovered that Restless Legs Syndrome had a higher prevalence in subjects suffering from 38 different inflammatory conditions.

This was the first study that really made a connection between Restless Legs Syndrome and inflammation.

It also became clear that Restless Legs Syndrome was not causing secondary conditions and that secondary conditions were not causing Restless Legs Syndrome. All conditions, including RLS, resulted from the underlying presence of inflammation.

For example SIBO does not cause RLS, and RLS does not cause SIBO. They both exist because of inflammation.

From their Summary:

"The fact that 95% of the 38 highly-associated RLS conditions are also associated with inflammatory/immune changes suggests the possibility that RLS may be mediated or affected through these mechanisms. Inflammation can be responsible for iron deficiency and hypothetically could cause central nervous system iron deficiency-induced RLS."

From their Conclusion:

"The etiology and pathophysiology of RLS is yet to be determined. Although specific genetic links are prevalent and CNS iron deficiency plays an important role in the pathophysiology, we do not know what triggers the iron deficiency or how most gene links are directly involved in the pathophysiology of RLS. In this unique syndrome there are many potential ways for the symptoms of RLS to occur including alternative causes such as peripheral neuropathy. Inflammation and immune alterations are prevalent in 95% of the highly-associated RLS conditions. This suggests the possibility that RLS may be mediated through these mechanisms.

There are three hypothetical mechanisms by which this can occur:

1) inflammation can trigger iron deficiency and this in turn is a well known trigger for RLS;

2) immunological reactions to bacteria or other unknown antigens may hypothetically trigger RLS by direct immunological attack on the central or peripheral nervous system;

3) altered host defenses based on genetic variants may predispose individuals to inflammation or an altered immunological response leading to RLS."

You can view the full study here:
https://www.sciencedirect.com/science/a ... 9211000980

I was doing my own personal (non medical) research at the time and had the good fortune of connecting with Doctors Weinstock and Walters. The bulk of my correspondence was with Dr. Weinstock.

The doctors were kind enough to provide me a quote for a website that I had launched with natural healing advice for RLS sufferers. The main premise of my website was that inflammation was the cause of Restless Legs Syndrome.

Considering that these two doctors are legendary in the world of RLS, these quotes carry a lot of weight.

Doctor Walter's comment is essentially a reiteration of their study's conclusion, but Dr. Weinstock uses a term that you NEVER hear from doctors stating "there is no doubt in my mind."

Here are the quotes:

"Our study suggests that RLS may be mediated through inflammatory or immunological mechanisms. Since inflammation is also associated with iron deficiency, these results are also in agreement with the iron deficiency hypothesis for RLS." - Dr. Arthur Walters, MD, Professor of Neurology, Vanderbilt Department of Neurology

"I have thoroughly analyzed every known scientific study that has been done on Restless Legs Syndrome. Taking all of this data into consideration, there is no doubt in my mind that inflammation plays a major role in the occurrence of RLS. I see this time and time again with many patient types." - Dr. Leonard Weinstock, MD, Certified in Internal Medicine and Gastroenterology, St. Louis, MO

[Frunobulax]

So I take it that leads somewhere? After all we're in "Non-prescription Medicines, Supplements, Diet".

FYI, if we DON'T need something then it's more authority proofs in medicine. I never witnessed such obedience anywhere else, if the bigwig doctor looks at something for 2 seconds and says something then all subordinates have to eat dirt, even if they have the opposite opinion. So I googled Weinstock and found a ton of "something is associated with something" studies. (I had never heard of him before.) Not a ringing endorsement as retrospective observational studies are the weakest of weak forms of studies, not able to give any proof but only useful to form conjectures. And actually wrong in the vast majority of all cases (see for example https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182327/, https://www.reuters.com/article/2012/03 ... P20120328/).

But anyway, maybe it's just me, but in my college days we had a rule that anyone who invokes an authority proof has automatically lost the argument in question, as she/he is out of valid arguments. So please, (a) post in the appropriate subforums, (b) if you link a study and claim that the full study is there then make sure it really is (the full study is behind a paywall, the "snippets" available contain such nuggets as "The etiology and pathophysiology of RLS is yet to be determined", groundbreaking insight!) and (c) no more quotes from "legendary" doctors. We've been around for a bit and we know who has a name in RLS research.

Anyway, even though inflammation is certainly associated with RLS (no doubt about that), the question is (a) is it causal and (b) if yes, what could you do about it.

[Rustsmith]

Sorry for the delayed response. Microsoft had my desktop computer tied up for half of the day yesterday doing updates so it took some time to be able to dig my way out so that I could get access to my university library account.

I was able to get a full copy of the paper by Weinstock, et al. and found that it is a great example of the need to read an entire publication and not rely upon just the short synopsis provided by search systems such as ScienceDIrect.

There were several things in the paper that I found very interesting. First was their statement that although their theory is that there is a linkage between RLS and inflammation, they do not have any idea why any of the the well established RLS meds (DAs, gabapentin, the opioids and benzos) should have any impact upon inflammation even though the admitted that these drugs are very effective.

They discussed a number of related conditions but surprisingly did not include Parkinsons, which sometimes has RLS occur as the disease worsens. They spent some time discussing MS (a condition that I have spent a lifetime following since my wife has had it since age 16). They seemed to assume that there is an inflammatory role in MS, which seemed to me to be stretching things a bit. MS is an autoimmune condition where the white blood cells have decided to attach the fatty mylein sheath around the nerves. Current research does not know why the white blood cells decide to turn on the body rather than attach the parasites and bacteria that they are supposed to. There is a theory that a latent virus, possibly measles, triggers this attack, but that is not known. Treatments that would reduce inflammation, such as steroids, sometimes help but often do not and definitely do not shut down the disease.

They described how any inflammation can increase hepcidin levels, which can block iron adsorption in the gut. That is nothing new and this can easily be measured with blood tests to check both hemaglobin and ferritin levels.

What I found most curious was this statement in the section about potential treatments, which assumed that their inflammation theory is valid.

Objective evidence of a generalized enhanced inflammatory/immunological response in RLS is currently lacking. This must first be shown. Subsequently, one important thing that will need to be tested in future work is whether or not therapeutic agents such as the dopaminergic agonists quell any inflammatory response in RLS which might be expected if the inflammatory/immunological hypothesis for RLS is correct

This seems like an out and out admission that their paper is presenting a theory that still needs a great deal of research before they could proceed to even investigate methods of attempting to treat their proposed root cause of inflammation.

I have two more points. The first is that this paper was published in 2012 and was first submitted for publication in May 2011. They made the statement that

The etiology of restless legs syndrome (RLS) is unknown.

I would suggest that the work by Dr Sergei Ferre at NIH in 2019 has established the etiology and that what needs to be done now is to investigate the various means by which iron fails to reach the substantia nigra at levels that we should have and whether a new safe form of treatment based upon Ferre's adenosine findings can be developed.

My second point is that other researchers since this paper was published have not seemed to pick up on it's suggested lines of additional study. I have personally written papers very much like this that proposed a new theory and suggested lines of research for others to follow. The difference is that my theories were later proven by other researchers, which is the way that science is supposed to progress. The fact that others have not published results on the lines of research suggested by Weinstock implies to me that either they were not persuaded by the thesis in his paper or else their studies failed to show meaningful enough results to warrant the effort of publication.

[Frunobulax]

My second point is that other researchers since this paper was published have not seemed to pick up on it's suggested lines of additional study. I have personally written papers very much like this that proposed a new theory and suggested lines of research for others to follow. The difference is that my theories were later proven by other researchers, which is the way that science is supposed to progress. The fact that others have not published results on the lines of research suggested by Weinstock implies to me that either they were not persuaded by the thesis in his paper or else their studies failed to show meaningful enough results to warrant the effort of publication.

That was my thought as well, it's quite possible that someone tried to do more studies and failed, and unfortunately failed studies are rarely published.

I found inflammation a rather interesting theory for quite some time now. Assuming that we should primarily target inflammation in the brain (as this is notoriously difficult to diagnose), and we know that most antiinflammatory drugs like NSAIDs can't cross the blood-brain-barrier (IIRC -- or at least are inefficient for brain inflammation), LDN (low dose naltrexone) should help with RLS as this is one of the few drugs that are efficient in the brain https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3962576/. But doctors are hesitant to prescribe LDN, especially to patients on opioids as naltrexone is an opioid antagonist.

I remember that dopamine agonists (and dopamine) appear to have anti inflammatory properties as well (found a discussion a while ago: viewtopic.php?p=106668#p106668). I just posted on Abilify/Aripiprazol (viewtopic.php?f=4&t=11472), low dose Abilify is suspected to have antiinflammatory effects in the brain as well, an effect that may disappear in the usual higher doses because it works as a partial dopamine agonist.

But this has been known for a while, and must be known at least to some RLS specialists. Weinstock is a member of the LDN research trust and should have had the possibility to do a study with LDN and RLS. Which brings me back to the possibility of failed studies.

At the very least I'll hopefully be able to give a n=1 result on low dose Abilify in a few months. (The usual procedure for LDA is that it takes a few months to reach the target dose, with a small dosis increase only every 1-2 weeks due to side effects and long half life.)

[Rustsmith]

Earlier today, I was reading a summary of research into Alzheimers that was intended for the general population. They discussed an inflammation theory for Alzheimers and mentioned how hard it is to get anti-inflammatory agents across the blood-brain barrier. They said that three groups were currently looking at the combined use of focused beam ultrasound with a specific anti-inflammatory drug that would target a type of inflammation fighting system in the brain that seems to go wild and then cause inflammation. The drug has difficulty crossing the blood-brain barrier, so the focused beam ultrasound is being used to poke small holes in the barrier. Sounds highly risky, but if we think RLS research has made little progress, Alzheimers has an absolutely horrible track record with almost zero successes in several decades.

[Frunobulax]

[...] if we think RLS research has made little progress, Alzheimers has an absolutely horrible track record with almost zero successes in several decades.

Possibly due to a wrong target of the interventions. There are plenty of researchers that argue that the amyloid plaques are just a defense mechanism of the brain and not the cause of Alzheimers, yet almost all drugs brought to trial focus to reduce the amyloid plaques and have limited success along with pretty bad side effects.

Which sounds eerily similar to the cholesterol/athrosclerosis issue, where it's easy to conjecture that cholesterol is the culprit, yet most interventions at lowering cholesterol have not only failed to reduce atherosclerosis events significanlty (10% or less reduction), but whenever all-cause mortality was measured it went up under the cholesterol-lowering interventions, except for very few special cases.

If an conjecture is that A causes B, and all interventions to reduce A fail to lower B significantly, then the conjecture is most likely wrong. So I'm very glad that Alzheimer research starts to look at other pathomechanisms and interventions.

[Rustsmith]

Possibly due to a wrong target of the interventions.

We are drifting off topic, but that was exactly one of the points that the article made. For too long, everyone studied ambloid plaques because that is what Dr Alzheimer first observed. They even observed that post mortem studies found that many patients they thought had Alzheimer's didn't have any plaques and so probably had a different form of dementia.

Only a small number of the recent studies have continued looking at plaques. Most now are looking more closely at tau tangles since these are more closely aligned with the areas where memory impairment and cognitive decline are occurring in most patients. Another area is looking at the development of blood tests that can be done in a doctor's office rather than the need for the PET scans or lumbar punctures that are currently required to diagnose early Alzheimer's.

[CalmLegsJL]

So I take it that leads somewhere? After all we're in "Non-prescription Medicines, Supplements, Diet".

FYI, if we DON'T need something then it's more authority proofs in medicine. I never witnessed such obedience anywhere else, if the bigwig doctor looks at something for 2 seconds and says something then all subordinates have to eat dirt, even if they have the opposite opinion. So I googled Weinstock and found a ton of "something is associated with something" studies. (I had never heard of him before.) Not a ringing endorsement as retrospective observational studies are the weakest of weak forms of studies, not able to give any proof but only useful to form conjectures. And actually wrong in the vast majority of all cases (see for example https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182327/, https://www.reuters.com/article/2012/03 ... P20120328/).

But anyway, maybe it's just me, but in my college days we had a rule that anyone who invokes an authority proof has automatically lost the argument in question, as she/he is out of valid arguments. So please, (a) post in the appropriate subforums, (b) if you link a study and claim that the full study is there then make sure it really is (the full study is behind a paywall, the "snippets" available contain such nuggets as "The etiology and pathophysiology of RLS is yet to be determined", groundbreaking insight!) and (c) no more quotes from "legendary" doctors. We've been around for a bit and we know who has a name in RLS research.

Anyway, even though inflammation is certainly associated with RLS (no doubt about that), the question is (a) is it causal and (b) if yes, what could you do about it.

I'm not sure what your issue is, but this is the right forum.

The whole point of me bringing up inflammation is because it presents the idea that RLS symptoms can be lessened. Most of this lessening can be done through natural remedies.

I know the trendy thing is to take horrible drugs that weren't created for RLS in the first place, and then kind of wait around for a medical breakthrough, but that's not going to happen.

Read the other studies I've posted that "suggest" that inflammation is the cause of Restless Legs Syndrome.

The thing is, you can keep taking your drugs while at the same time, developing an anti-inflammatory strategy.

No one is trying to take your drugs away.

And more studies will be coming out that suggest the same thing, you can be certain of that.

[Frunobulax]

I know the trendy thing is to take horrible drugs that weren't created for RLS in the first place, [...]

No one is trying to take your drugs away.

I find it fairly offensive that you throw _that_ in my face. You really have no idea how I have suffered from drug side effects (but this is a private matter). But yes, I still consider drugs as a tool in the toolbox, to be used when appropriate. I'd be a fool if I wouldn't do that.

But in fact I have suggested inflammation as RLS cause many years ago. Let me repeat my questions, since you chose to ignore them. (a) Is inflammation causal? and (b) if yes, what do you suggest we do about it? Because fighting systemic inflammation is hard, and very few of the available (and often pricey) remedies actually make a difference. Also keep in mind that a lot of the readers here have literally tried anything under the sun.

It's always interesting to throw around theories, but it's less interesting if they have been thrown around dozens of times already (like inflammation) and even less if they have no practical implications.

[CalmLegsJL]

I know the trendy thing is to take horrible drugs that weren't created for RLS in the first place, [...]

No one is trying to take your drugs away.

I find it fairly offensive that you throw _that_ in my face. You really have no idea how I have suffered from drug side effects (but this is a private matter). But yes, I still consider drugs as a tool in the toolbox, to be used when appropriate. I'd be a fool if I wouldn't do that.

But in fact I have suggested inflammation as RLS cause many years ago. Let me repeat my questions, since you chose to ignore them. (a) Is inflammation causal? and (b) if yes, what do you suggest we do about it? Because fighting systemic inflammation is hard, and very few of the available (and often pricey) remedies actually make a difference. Also keep in mind that a lot of the readers here have literally tried anything under the sun.

It's always interesting to throw around theories, but it's less interesting if they have been thrown around dozens of times already (like inflammation) and even less if they have no practical implications.

I'm still not sure of your question. The inflammation behind restless legs can be cause by an unlimited number of things. Most likely chronic inflammation results from a combination of factors. Diet, environment, stress, genetics (which can be changed via epigenetics), electronics etc.

As the inflammation inside the body grows it is destined to manifest as a "medical condition." This can be anything from cancer to IBS.

If the actual inflammation is not treated, it will continue to grow and manifest as additional conditions.

I'm pretty sure most of the people on this board have more than RLS as a medical condition.

Depression, anxiety, IBS, lupus etc.

I'm just guessing, but that's what I believe.

This is where the idea of RLS being a biomarker comes in. It's a SIGNAL to you from your body that this inflammation needs to be tended to.

Pharmaceuticals are not the answer. They address they symptoms.

The underlying inflammation must be addressed via diet, relaxation as well as additional modalities that are available that help to lessen inflammation.

And one last thing. When someone says they've tried everything, they haven't. Inflammation is a very personal affliction, but there are no cases that are beyond repair.

The key is to find what works for each individual. For instance, for one individual tomatoes are inflammatory, for another person they are anti-inflammatory.

Meditation, EFT, supplements, therapy, herbs, red light therapy, yoga/stretching, acupuncture, cupping, early morning lemon water, early morning celery juice, exercise and energy balancing are examples of helpful aids to lessen inflammation.

[Frunobulax]

Look, I appreciate it that you try to bring something into the forum that you believe should be discussed. But we must be very careful in making sure that people draw the right conclusions. I agree that it's important to reduce inflammation (and find the underlying cause), but it's not at all trivial to do so. Inflammation doesn't come out of the blue, there is a root cause. So if you believe that inflammation causes your RLS, then you need to find and fix the root cause. And our medical system is not set up well for that, because it requires to find the root cause, and the vast majority of doctors don't even look for root causes if you have a chronic disease. So essentially we patients need to become our own doctors, and that's a tall order.

My question (a) is the one question that should always be asked in (or after reading) retrospective observational studies. If A is correlated with B, then it may be that A causes B, B causes A or both are independent but have a common cause. (Large belt sizes correlate with obesity. Clearly large belt sizes are not causal for obesity.)

Many observational studies suggest causation, but get it wrong quite often. These studies can only ever form a conjecture. The very rare exception is for example smoking and lung cancer, where studies found that smokers have a 20fold or even 30fold chance of getting lung cancer. That's causation all right, but you need an effect size large enough.

But to give you a more interesting example: High cholesterol is associated with atherosclerosis, but the association is a fairly weak one. For example, only 23% of hospital patients with coronary artery disease have elevated cholesterol levels (https://pubmed.ncbi.nlm.nih.gov/19081406/). Also there is the fact that the higher your cholesterol, the longer you live (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4908872/). Still, pharma and media have been relentlessly beating the drum of "lower your cholesterol". (Which was very lucrative for some food and pharma companies, just a really weird coincidence I'm sure.) But to prove causation, you'd need to show that lowering cholesterol levels actually prevents atherosclerosis (which would be an interventional study). This has been tried and failed numerous times (intervention studies see very small reductions in strokes and heart attacks, but a rise in total mortality, indicating that lowering cholesterol will make you die faster https://doi.org/10.1016/j.amjmed.2018.04.027). Hence high cholesterol is (in my personal opinion) not causal for atherosclerosis, even if we only look at the supposedly "bad" cholesterol (https://doi.org/10.1080/17512433.2018.1519391).

And that's the way it goes very often in studies. A conjecture is made from observational studies, but later evidence proves the conjecture wrong. That's why most studies will use a lot of weasel words and be very careful to suggest causation (because this increases the chance to get published) while leaving a lot of backdoors open that it's not causation at all.

Coming back to RLS, I agree that inflammation strongly correlates with RLS. But that does not prove causation, it could be a common cause between inflammation and RLS. You could prove causation by doing an interventional study that shows that reducing inflammation also reduces RLS (which is oversimplified because we'd have to give a good definition of "inflammation" -- high CRP, high cytokines, brain inflammation and so on). A weaker approach are animal models, for example if you cause inflammation in rats, does this impair their sleep in a pattern associated with RLS?

So my question (a) is if there are any studies supporting that inflammation causes RLS. If RLS is truly a biomarker for inflammation, then there should be studies proving that. I only heard about single cases, which (like observational studies) can be used to formulate a conjecture, but nothing more. As far as I know we only have a conjecture here, because we have neither proven nor disproven it either way.

My question (b) is about practical therapeuthic consequence. You name some things (and I agree with them), but for example in regard to diet there is no consensus what is inflammatory. (Personally I avoid carbs, lectins and oxalates along with some things I'm allergic to, and I have good reasons for doing so and posted these in this forum. I believe the diet allowed me to reduce my oxycodone, but a reduction from 30mg to 20mg was the best I could achieve. But there are plenty of people who'd argue that my diet is dangerous and unhealthy, you'd have to go vegan or low fat, for example, to reduce inflammation.)

IMO the answer could either be (1) good quality interventional studies (double blind, placebo controlled) showing success in reducing RLS, and (2) n=1 reports (I have done something and it worked for me). For example we have plenty of reports that a low oxalate diet helps some people, but I am very low oxalate (<50mg) now for over a year and I've been low oxalate (<200mg) for about 4 years, and while my RLS worsens if I consume more oxalates, it doesn't go away by cutting out oxalates. So clearly reducing oxalates is worth a try, but it wasn't the answer for me.

[CalmLegsJL]

Look, I appreciate it that you try to bring something into the forum that you believe should be discussed. But we must be very careful in making sure that people draw the right conclusions. I agree that it's important to reduce inflammation (and find the underlying cause), but it's not at all trivial to do so. Inflammation doesn't come out of the blue, there is a root cause. So if you believe that inflammation causes your RLS, then you need to find and fix the root cause. And our medical system is not set up well for that, because it requires to find the root cause, and the vast majority of doctors don't even look for root causes if you have a chronic disease. So essentially we patients need to become our own doctors, and that's a tall order.

My question (a) is the one question that should always be asked in (or after reading) retrospective observational studies. If A is correlated with B, then it may be that A causes B, B causes A or both are independent but have a common cause. (Large belt sizes correlate with obesity. Clearly large belt sizes are not causal for obesity.)

Many observational studies suggest causation, but get it wrong quite often. These studies can only ever form a conjecture. The very rare exception is for example smoking and lung cancer, where studies found that smokers have a 20fold or even 30fold chance of getting lung cancer. That's causation all right, but you need an effect size large enough.

But to give you a more interesting example: High cholesterol is associated with atherosclerosis, but the association is a fairly weak one. For example, only 23% of hospital patients with coronary artery disease have elevated cholesterol levels (https://pubmed.ncbi.nlm.nih.gov/19081406/). Also there is the fact that the higher your cholesterol, the longer you live (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4908872/). Still, pharma and media have been relentlessly beating the drum of "lower your cholesterol". (Which was very lucrative for some food and pharma companies, just a really weird coincidence I'm sure.) But to prove causation, you'd need to show that lowering cholesterol levels actually prevents atherosclerosis (which would be an interventional study). This has been tried and failed numerous times (intervention studies see very small reductions in strokes and heart attacks, but a rise in total mortality, indicating that lowering cholesterol will make you die faster https://doi.org/10.1016/j.amjmed.2018.04.027). Hence high cholesterol is (in my personal opinion) not causal for atherosclerosis, even if we only look at the supposedly "bad" cholesterol (https://doi.org/10.1080/17512433.2018.1519391).

And that's the way it goes very often in studies. A conjecture is made from observational studies, but later evidence proves the conjecture wrong. That's why most studies will use a lot of weasel words and be very careful to suggest causation (because this increases the chance to get published) while leaving a lot of backdoors open that it's not causation at all.

Coming back to RLS, I agree that inflammation strongly correlates with RLS. But that does not prove causation, it could be a common cause between inflammation and RLS. You could prove causation by doing an interventional study that shows that reducing inflammation also reduces RLS (which is oversimplified because we'd have to give a good definition of "inflammation" -- high CRP, high cytokines, brain inflammation and so on). A weaker approach are animal models, for example if you cause inflammation in rats, does this impair their sleep in a pattern associated with RLS?

So my question (a) is if there are any studies supporting that inflammation causes RLS. If RLS is truly a biomarker for inflammation, then there should be studies proving that. I only heard about single cases, which (like observational studies) can be used to formulate a conjecture, but nothing more. As far as I know we only have a conjecture here, because we have neither proven nor disproven it either way.

My question (b) is about practical therapeuthic consequence. You name some things (and I agree with them), but for example in regard to diet there is no consensus what is inflammatory. (Personally I avoid carbs, lectins and oxalates along with some things I'm allergic to, and I have good reasons for doing so and posted these in this forum. I believe the diet allowed me to reduce my oxycodone, but a reduction from 30mg to 20mg was the best I could achieve. But there are plenty of people who'd argue that my diet is dangerous and unhealthy, you'd have to go vegan or low fat, for example, to reduce inflammation.)

IMO the answer could either be (1) good quality interventional studies (double blind, placebo controlled) showing success in reducing RLS, and (2) n=1 reports (I have done something and it worked for me). For example we have plenty of reports that a low oxalate diet helps some people, but I am very low oxalate (<50mg) now for over a year and I've been low oxalate (<200mg) for about 4 years, and while my RLS worsens if I consume more oxalates, it doesn't go away by cutting out oxalates. So clearly reducing oxalates is worth a try, but it wasn't the answer for me.

"Look, I appreciate it that you try to bring something into the forum that you believe should be discussed. But we must be very careful in making sure that people draw the right conclusions."

I appreciate that you're being cautious and protecting the members of this forum from potentially false information.

All I'm doing is providing an option based on my own experience (an option that has helped many people).

People can decide on their own whether it's something they want to explore or ignore.

There's no risk, and no side effects.

I've provided 3 studies that strongly suggest that inflammation is at the core of RLS. As I stated, more will come.

However, in the world of Big Pharma this is a loser proposition. Big Pharma doesn't have anti-inflammatory that does more good than harm, so there's no reason to pump a lot of funding into this kind of research.

I'm grateful for the few studies that have so far.

[Frunobulax]

You provided one link to a study here which shows association but not causation, and even the summary is as careful as I've ever seen with "suggests the possibility that RLS may be mediated or affected through [inflammation].". So which 3 studies prove causation?

"More will come" is not a valid argument, sorry. If we know something then we don't need studies, if we need studies then we can't be sure what the outcome will be.

True story: "Don't worry we'll prove it" was the argument in the 1960s when the cholesterol craze started, "studies are being made and they will prove the lipid hypothesis". The first part was true, studies were made, and the results contradicted the assumption (like the Sydney Heart Study) and were never published, or published 40 years later when the original data was discovered after one of the researchers passed away. Or the studies just stated that they support the lipid hypothesis while the data actually contradicted it (like the MRFIT study). Or they just left out the inconvenient stats (like all cause mortality) and published only the results they liked.

[CalmLegsJL]

You provided one link to a study here which shows association but not causation, and even the summary is as careful as I've ever seen with "suggests the possibility that RLS may be mediated or affected through [inflammation].". So which 3 studies prove causation?

"More will come" is not a valid argument, sorry. If we know something then we don't need studies, if we need studies then we can't be sure what the outcome will be.

True story: "Don't worry we'll prove it" was the argument in the 1960s when the cholesterol craze started, "studies are being made and they will prove the lipid hypothesis". The first part was true, studies were made, and the results contradicted the assumption (like the Sydney Heart Study) and were never published, or published 40 years later when the original data was discovered after one of the researchers passed away. Or the studies just stated that they support the lipid hypothesis while the data actually contradicted it (like the MRFIT study). Or they just left out the inconvenient stats (like all cause mortality) and published only the results they liked.

This from a person taking a drug(s) not created for the condition of RLS prescribed by a doctor that has no clue what causes RLS.

So just how dedicated to pure science are you?

Doctor Weinstock, who is one of the world's greatest experts on RLS (whether you've heard of him or not) said "there is no doubt in my mind that inflammation plays a major role in the occurrence of RLS."

That's pretty clear.

Why not let people decide for themselves instead of you stomping over everything I post?

[Rustsmith]

Since this thread cannot seem to come to a conclusion and since Dr Weinstock is repeatedly cited as "one of the world's greatest exterts on RLS", I decided to use the same tools to investigate him that I would if I saw a citation in my own field of study from someone that I had never heard of before.

What I found was that Dr Leonard Weinstock is a Gastroenterologist with the University of Washington in St. Louis, Missouri. He has a number of publications, but the majority of them have to do with Irritable Bowel Syndrome (IBS), Crohn's Disease and SIBO. Out of all of his publications the only ones on RLS that did not exclude anyone that did not also have IBS or SIBO were the one cited above, one where he found no correlation be Long Covid and RLS and one or two where he tried to use Low Dose Naloxone to treat RLS (a fad about 10 years ago that went no where).

There is no question that any intestinal condition that limits iron adsorption is going to have a correlation with RLS. I have a friend with severe Crohn's and he struggles just to get general nutrition, much less a proper balance of vitamins and minerals (like iron).

What I found interesting was what was missing from his list of publications. Often, holes in investigational data can be just as important as what appears (negative proofs). In the case of Dr Weinstock, he is located in the same town the current president of the RLS Foundation, a doctor who is a leading pediatric RLS expert as well as an RLS researcher and who also has RLS herself. Why did Dr Weinstock find it necessary to have Dr Walters (of Vanderbilt University) co-write his publication? My guess is that he simply needed Dr Walter's to contribute his expertise in the then current understanding of the role of genetics in RLS.

This from a person taking a drug(s) not created for the condition of RLS prescribed by a doctor that has no clue what causes RLS.

Personal attacks are not appropriate. Please stick to the points that you wish to make.