Just getting around to reading this Topic now, fascinating as always. I have limited energy this time of night so kind of point-form notes on some of the things you covered, just as the thoughts came into my head as I was reading.
I was wondering if someone has tried to observe basic biomarkers and correlate them with RLS severity. For example, has anyone tried to correlate blood sugar, insulin, triglycerides, cholesterol with RLS severity? Do we know if RLS patients tend to have high uric acid?
Not to my knowledge, but it would be good to have something basic like that done.
consequences of insulin resistence, mechanics of silent inflammation and the role of carbohydrates (which we eat a lot more than 50 years ago) and polyunsaturated fats (the vegetable oils that are now omnipresent in kitchens). Could RLS be caused along the same mechanisms?
one route could be thru changes to gut microbe population (carbs = bad bugs = bad bug poop (sorry, metabolic by-products) that gets in your blood = problems in potentially any system, including neurological e.g. WED/RLS).
The polyun fats would cause the problem via a different route - sucking up our bodily resources to deal with the resulting [ouch I forget what nasty things oxidized oils cause in our bodies] nasty things, I guess I'll say. And our bodily resources - by which I mean here the molecules that do our cellular metabolism - are limited by diets lacking in micronutrients.
Inflammation is driven by reactive oxygen species (ROS), which do affect the iron metabolism even though many details are fairly unclear (https://www.ncbi.nlm.nih.gov/pmc/articl ... 415455.pdf
). But we do know that inflammation raises ferritin values, and it is possible that iron stores are depleted by ROS (after all, iron does react with those ROS like H2O2). Thus, we may have a pathway inflammation/oxydative stress -> low iron stores, but I'm very unsure about this.
Nice line of reasoning. Does not account for the iron deficiency being localized to the brain, though.
iron IVs would solve the visible problem (RLS) but may cause damage because it exacarbates the original problem, possibly a silent inflammation?
I have thought often that I might be causing a bigger problem down the road! haha. But I don't think BID is a protective response (I haven't thought thru why). Maybe partly because of the awesome restoration of refreshing sleep I've had since my infusion took effect, and my general sense of well-being; even if I knew that the BID was a protective response, I probably would choose to get the infusion - I'd rather live well now and die sooner than live like I did for the past 12 years.
lso Omega-3 is antiinflammatory, but instead of a 1:1 relation between PUFAs and omega-3 fatty acids (as it used to be when we were hunters and gatherers) we're up to 20:1 or so
I think you mean "between omega-6's and omega-3's
". They're both polyunsaturated.
They would literally eat vegetables only if they were starving, so they didn't get any vitamin C or whatever in their body,
I'm not an expert but I'm not sure about this. The Inuit made various teas from local plants, some of which are rich in vitamin C. Also, the Dene ("Indians" who live in northern Canada) would eat the stomach and small intestine contents of the caribou they caught; Inuit may have done the same. Also, I've had Inuit people show which little tundra plants were edible. I didn't ask about the lifesyles of their great-grandparents, but the fact that they showed me such things implies a cultural use for the plants.
I'm totally on board with your general thesis, that inflammation might be invovled in WED/RLS, and that diet can have huge effects over time, negative or positive.
Unfortunately, many medical researchers today adapt the laywers view too. This can be evidenced especially in nutritional science.., but also in Alzheimer research...
Too true! Not just today, unfortunately. Even Mendel is suspected of bias (perhaps subconscious) in his classic experiment with pea plants that helped establish his theory of genetic inheritance - his data are too perfect. But modern nutritional "science" has been full of it! The guy who started the saturated-fat scare comes to mind, and the whole
(2) BID may cause RLS symptoms. There is some biochemic reasoning for (2), that is, we have an idea why iron deficiency would mess with dopamine production.
I don't know if you have these two papers from various of Arthur Walter's colleagues:
Ye-Ming J. Sun and others, 2011, Opioids protect against substantia nigra cell degeneration under conditions of iron deprivation: A mechanism of possible relevance to the Restless Legs Syndrome (RLS) and Parkinson's Disease. Journal of the Neurological Sciences v. 304, p. 93-101.
Shangru Lyu and others, 2019. Hyperactivity, dopaminergic abnormalities, iron deficiency and anemia in an in vivo opioid-receptors knockout mouse: Implications for the restless legs syndrome. Behavioural Brain Research v. 374, p.1-9.
These papers take it back a step further and suggest that an opioid deficiency might underlie the iron deficiency (2019 paper) and that opioids protect dopaminergic cells from iron deficiency (2011 paper). (very overimplified. They were dealing with mice (2019) and with cultered cells from a rat brain (2011).
The general thinking out there is that BID is part of WED/RLS. I don't think anyone has pretended to have determined cause and effect yet. But people are poking away at it. I like the opioid research, because it needs to be a part of the picture. The fact that opioids work to resolve symptoms can't be ignored without compromising the search for causes and mechanisms.
I'm not making a case that inflammation is the only thing that causes RLS, I am making a case that we should look at this theory.
You're in the same boat as with BID - if inflammation is the "cause", what caused the inflammation? There is a bigger picture here.
The rapid fluctuation of WED/RLS symptoms could be caused by the interaction of various bodily states with the low brain-iron state, including inflammation.
the first step is to see if there is correlation (which I find highly probable)
If WED/RLS is correlated with inflammation, why aren't ferritin concentrations high in all of us? Though I suppose an answer could be that not all forms of inflammation drive ferritin to increase.
Try to do systematic, long-term experiments with diet. Get 2 groups, put one group on a low carb high fat diet with mostly saturated fats and no polyunsaturated fats, and see if it makes a difference for 2 years. Possibly get a third and fourth group that do the same with intermittent fasting,
This needs to go farther. Micronutrients are essential to the smooth functioning of every cell - of every mitochondrion in every cell, and our bodies can;t carry out the processes of life without an adequate supply of them. For example, our bodies need micronutrients to eliminate toxins that we eat or breathe, or that get created by metabolic processes that have to use an inefficient pathway for lack of an essential nutirient required to make a molecule needed on the efficient pathway.
The diet experiments (excepting the controls) should include a healthy variety of micronutrient source foods, and eliminate all foods that cause stress in the body.