Brain iron deficiency vs. functional medicine

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Brain iron deficiency vs. functional medicine

Post by Frunobulax »

This one is in part triggered by the inflammation theory (viewtopic.php?f=5&t=10785). I should point out that I have strong views about some things, yet this is my personal opinion and I'm not a doctor. And of course (as with any texts on the internet) medical issues must be discussed with your doctor and this does not constitute medical advice.

To get to the point: I think we're focusing way too much on symptoms and not enough on root causes. If a treatment relieves a symptom, we think we have cured the disease. This is true in some cases, but often it's wrong. There is a reason, a root cause why we became sick, and most "root causes" will cause more than one symptom. And there are many cases where an isolated symptom can be eliminated with a treatment that does not fix the root cause. (Examples later.) But if we can fix the root cause, all the symptoms go away. I'll get to RLS in a moment, but please bear with me as I'll have to explain my approach a bit.

My approach here is "functional medicine" or "holistic medicine". Now the big problem with these terms is that they have been hijacked by quacks, and many people think of aluminium hats if they hear these terms. But when you get down to it, they only mean that we have to look at the root cause of a problem and try to fix that. And I'd argue that many people who claim to do functional medicine do exactly the opposite, because they ignore proper science. We need evidence-based science to find the root cause for a group of symptoms, and biochemistry and studies to see what fixes them.

1. Our traditional medicine has made great achievements in the past. The average life expectancy has doubled in the last 200 years. The reason is that we have found the root cause for many diseases that killed us back then: We can treat many infections (with antibiotics) and fix most traumatic injuries (we can mend bones and replace joints). We can inoculate against many viruses (which again fixes the root cause for the disease, as we essentially prevent the virus to replicate if we get infected). And in acute medicine we do "functional" medicine all the time: Treating a bacterial infection with aspirin is symptom based (lower the fever), treating it with antibiotics is functional (fight the root cause, the dangerous bacteria). Immobilizing a torn tendon to let it heal (or repair it surgically) is functional medicine, because it allows the body to heal the damage. Functional medicine is not "alternative", on the contrary. Our traditional medicine is "functional" in many respects. But not always. And herein lies the rub.

2. The problem is that we abandon this functional approach when we get to chronic diseases, often because we don't know the root causes. I think the most spectacular failure in this regard is type 2 diabetes (where we actually know the root cause but don't fix it), for which there are a lot of very good videos and articles out there (maybe check out But this gets too far off topic, so I'll use another example with a RLS connection: Heartburn. We get it if stomach acid leaks into the esophagus. It can happen occasionally if we eat too much (like mechanical pressure pushing some stomach contents up), which is not a big problem. But if we get it chronically (GERD), the "seal" between the stomach and the esophagus does not work properly. The usual treatment is to lower stomach acid, often using PPIs (proton pump inhibitors) which reduce the "level of acidity" dramatically. And that's completely wrong (in my opinion), the problem being that we need our stomach acid to digest food (especially protein, which we can't break down without stomach acid - there are cases of people who are severely deficient in some amino acids even though they eat plenty of protein because they simply can't process them in the gut) and kill bacteria that we ingest every time we put something in our mouth. Less obvious but equally severe is the fact that we need a balanced gut microbiome (the bacteria in our gut aid our immune system and extract vitamins and minerals for us from our food), and we cause a degradation if stomach acid is low: We get less of the "good" bacteria and more of the "useless" or even harmful bacteria (like helicobacter pylori). Also, those "proton pump inhibitors" tend to inhibit not only the proton pumps that produce stomach acid, but other proton pumps (but I won't go into detail here). The long-term result are deficiencies, most notably in vitamin B12, calcium and iron (RLS!), I wrote on this in another thread: viewtopic.php?f=4&t=10519. And the big problem is that these deficiencies will take many years to show up. At first we seem to have no side effects at all, but 10 years down the road we gradually develop unspecific symptoms (like restless legs, sleep disorders, depression etc.).

So instead of fixing the valve between stomach and esophagos, we lower the stomach acid. We relieve the symptoms and think we got rid of the disease, but cause another long-term disease instead by doing so. And in a spectacular manner: I don't have the US numbers, but in Germany (I'm a Kraut) more than 12% of the general population (and most likely 25% of all people over 40) take PPIs daily, a drug that has been around for just 30 years and that no one did any long-term studies on. In the last 5 years PPIs have been linked to several dozens of diseases including atherosclerosis, depression, brittle bones and dementia. A lot of these associations are controversial (some studies show a connection, others don't), but if only a small number of them are correct then PPIs are pretty toxic in the long term. (It's no problem to take them for a couple of weeks, just don't take them longer.)

The correct treatment (in my opinion) is to restore the valve function. Fundoplicatio surgery does the trick, but it has its risks and the effect is often not permanent. The better approach is non-surgical. And here is the most likely root cause via two mechanisms: And lo and behold, a low carb diet (no sugar, no carbs) fixes heartburn in 100% of the subjects according to studies, a success rate that no drug has ever achieved (, A diet based approach to the problem has no side effects and fixes the root cause.

3. Let's get back to RLS, and my issues with the BID. I do think that iron deficiency in the brain is the most likely cause for RLS (I'm open to different explainations as long as we haven't established the exact mechanism, but BID is the best candidate right now), but I disagree somewhat about the treatment (iron infusions). And here's why.
I can think of 3 root causes for BID:
  1. We have an *isolated* problem with iron uptake, perhaps for a genetic reason. In this case, iron IVs are the appropriate treatment (and really the only one that works). However, I'd expect this to be really, really rare, and affected people should show severe symptoms in early childhood (like anemia).
    The problem should be obvious in the usual iron blood markers (low ferritin, low transferrin saturation).
  2. There is not enough iron in our diet, or we have other "digestive" issues that block iron uptake (for example low stomach acid due to PPIs, or possibly leaky gut). Here it is most likely that iron deficiency is just one of many problems, we'll likely have other deficiencies/imbalances. Iron IVs may fix RLS for a while, but there will be other symptoms that are not addressed. The treatment that I would suggest is twofold: A one-time iron IV treatment (may be several infusions of course) to relieve the RLS symptoms, but then evaluate your diet and have your gut checked out (microbiome diversity, stomach acids etc.). If you fix the iron uptake issues, you shouldn't need a second IV. (Fixing gut issues is tricky though, and may take time. The most important step is probably to get rid of sugar and processed food. Eat "real" food made from freshly cooked ingredients that are not canned, frozen, dried or in other way processed.)
    Again I'd expect to see low iron blood markers here.
  3. There is enough iron in our system, but it doesn't get where it's needed. Up to 50% of RLS sufferers do not respond to iron IVs, and I'd expect most of them to be in this category. For these people blood iron markers will be good, and iron IVs show little to no effect. (I'm in that category.)
    You could call this branch "Else". Forgive my mathematical term here, but things start to get murky here - we don't have established root causes for this. However, this is where I see inflammation as the most likely reason (as stated in viewtopic.php?f=20&t=10588). More precisely, I'd expect that inflammation causes RLS for many sufferers with good iron values, and I think viewtopic.php?p=102630#p102630 makes a very good case for it. But there may be people where a localized iron deficiency is caused by other reasons. We need more research.
4. Finally, let me point out one alternative to the BID: The lack of iron could be a consequence of whatever causes RLS (possibly something that consumes iron in the brain) and not the cause. (Again, the search for the root cause. I'm not sure that it's really iron deficiency. Correlation does not imply causation.) I'm juggling probabilities here of course. I'm not fully convinced of the BID (even though I think it's the most likely explaination), therefore I will be open to this alternative and give it some thought.

Think of it this way: If iron is the fire brigade, lack of iron may cause a burning house to burn down. But if we have enough iron, we will quench the fire (fix the symptom) but end up with some damage (barbecued furniture). It would be better to prevent the fires altogether (fix the root cause).

A more medical analogue would be oxidative stress: Antioxidants like vitamin D/E or alpha lipoic acid will reduce oxidative stress. If we become deficient in antioxidants, we will experience severe symptoms (autoimmune diseases). But supplementing these antioxidants will only improve some of the symptoms, because the oxidative stress (free radicals) is still produced by our immune system and causes damage before the antioxidants kick in. (That's essentially the mechanism how our immune system fights unknown invaders: They do some chemical warfare, and the antioxidants clean up afterwards.) The case could be similar for iron, in that it is needed to "clean up the mess".

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Re: Brain iron deficiency vs. functional medicine

Post by inflammatory_rls »

I fully agree with this post, and the points raised here explain why I am so interested in determining the root cause of RLS. It's reminiscent of the ending to the Wizard of Oz - early research into RLS indicted dopamine, but later research found iron deficiency behind the curtain. What's behind the curtain of iron deficiency? Even if we find inflammation, what's behind that?

I also often think that whatever causes RLS must be causing other changes to my brain, changes that I am not even aware of. The underlying problem almost surely has multiple symptoms, of which RLS is only one. But those other symptoms are difficult to recognize. We can sense RLS because of the sensory experience, but what about damage to the brain without an accompanying physical manifestation? The brain does not experience itself. As Chesterton said, "the one created thing which we cannot look at is the one thing in the light of which we look at everything."

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Re: Brain iron deficiency vs. functional medicine

Post by QyX »

I think the "root cause" in many cases is simply the genetic makeup (talking about those with primary RLS who developed symptoms early). Things are maybe only slightly off balance as a child but the older you get, things get more and more out of whack. Over time this process accelerates and will affect more and more systems until you develop symptoms.

Environmental factors can either contribute to this development or delay it.

Then there is also constant mutation going on and not all of them are detected and repaired by the body. So I don't think that with systemic, complex disorders like RLS there is one single root cause.

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Re: Brain iron deficiency vs. functional medicine

Post by Rustsmith »

I think that virtually all RLS researchers would agree with your root cause point. We know that brain iron deficiency is the source of our symptoms, but that we do not always know the reason for this deficiency. For some people, the cause of iron deficiency is obvious, such as pregnant women and dialysis patients. In other cases, it is due to anemia but the cause of the anemia may or may not be obvious. Dietary deficiencies and gut issues (e.g. SIBO, Celiac disease and Chron's disease) are two possible sources.

But as you point out, for around 50% of us, iron supplementation (oral or IV) simply doesn't help. This may be due to some genetic issues, but why? There was a Foundation webinar presented recently by Dr. James Connor of Penn State where he discussed research that is looking at the mechanism of iron transport across the blood-brain barrier. It turns out even the researchers were surprised at how complex this mechanism is turning out to be. It is not as simple as a ferritin molecule passes through the capillary wall to deliver iron to the brain. It appears that the ferritin enters the epithelial cell and is broken down in the cell. The iron then undergoes some chemical transformations and then is sort of repackaged before being transferred into the brain. They are not sure yet, but one theory is that this process uses proteins that are formed using coding from the MEIS1 gene (which has the highest correlation to RLS of the 20+ genes that have been identified). If so, then this would present yet another cause of brain iron deficiency and could explain why some of us have low brain iron in spite of having high levels of iron in the bloodstream.

Therefore, I would not be surprised if all this ends up being a bit like a tree. We have a number of various RLS symptoms and degrees of severity, which would be represented by the branches and leaves of the tree. The chemical mechanisms in the brain that are driven by iron deficiency (dopamine receptor downregulation, glutamate receptor downregulation, and adenosine receptor downregulation) would be the trunk. Brain Iron deficiency would be the base of the trunk since it causes all the receptor downregulation and then there could be a myriad of sources of brain iron deficiency. As such, there would not be one root cause for everyone but there would probably be only one root cause per patient. Only some of these root causes would be treatable. And unfortunately for those of us with a genetic driven cause, treatment is probably something that will not occur during my lifetime even if we do learn exactly how genes such as MEIS1 are causing our RLS.

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Opinions presented by Discussion Board Moderators are personal in nature and do not, in any way, represent the opinion of the RLS Foundation, and are not medical advice.

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