Restless Legs Syndrome (RLS) Discussion Board

I have gotten almost complete relief from RLS by following a low oxalate diet. I have been reading some of the scientific studies and trying to come up with a possible explanation for what is happening in my body when I experience an episode of RLS. However, before I share my ideas I want to make clear that my version of a low oxalate diet includes avoiding glycine supplements, gelatin and gelatinous soups and stews because these foods stimulate my liver to produce oxalic acid endogenously.

Because researchers have established that low levels of iron in the brain and cerebro-spinal fluid may exist in all RLS sufferers, I assume that condition pertains to me. And I assume I have a low ferritin level. However, the fact remains that, without addressing those particular bio-markers in any significant way, I have achieved almost complete relief of symptoms. And, when I do “slip up” and trigger an RLS episode, the discomforts arrive on the day following the dietary mistake and last less than 24 hours.

My theory is that my body’s chronic low iron level makes it critical that my body’s systems do an impeccable job of distributing iron to all the places where it is needed every day. And the oxalate/oxalic acid interferes with that daily distribution.

Iron is typically bound to transferrin (the body’s distribution vehicle) with carbonate. However, oxalate can take the place of carbonate as the binding agent. Scientists have found that when oxalate takes the place of carbonate the bound iron is “locked up” so that it doesn’t release from the transferrin and, I assume, distribution is not accomplished.

Because our bodies have a greater iron binding capacity than we use on any given day, mine is able to bring additional resources into service and correct the situation within 24 hours, assuming I eat correctly on that second day. It might even make sense to say that the unpleasant sensations in my legs are a signal from my body to get me to move around and increase circulation in order to expedite the restoration of normal iron distribution.

I think it is critically important that scientists look more closely at the mechanisms which lead to the liver producing inappropriate amounts of oxalic acid. Some people are attempting to raise their ferritin level by taking ferrous bisglycinate and vitamin C. My experience is that glycine stimulates production of oxalic acid. And vitamin C supplements are widely recognized as stimulating its production also. I think we may also find that the augmentation which some people experience while taking Pramipexole and similar drugs is due to stress on the liver and a resulting endogenous production of oxalic acid.

Some scientists are dismissive of the idea that oxalate will take the place of carbonate in iron binding function in the “neutral pH of the blood.” It seems logical that the inappropriate production of excess oxalic acid may disturb the pH of the blood. The displacement of carbonate may eventually be seen as a protective mechanism that helps to maintain a proper pH of the blood because it helps to “mop up” the excess oxalate.

As always, I wish you all the best. Jim Hejl

An interesting model. What happens when we fast? Fasting would be similar to eating or producing oxalates with the iron, except worse, because there would be no iron available. So the WED/RLS would get worse the longer we fasted. Has anyone done a multi-day fast? Did your WED/RLS get better, worse, or no change?

I regularly do 20 hour fasts. Doesn't impact my symptoms. I have done a few longer fasts - up to 36 hours, but not many. Didn't notice any impact.

Jim, thanks for sharing your dietary management of RLS and it's impact on liver. Can you share more info on what that low oxalate fiet is like?
Since you mention liver and according to other comments RLS shows a high correlation w Diabitus 2. I wonder if there is any relationship if RLS with hepetatis or patients who had hepatitis earlier in their lives.
I am brand new to this discussion group and very thankful to benefit from everyone’s wisdom!

EVogel wrote: ↑

Sat Sep 04, 2021 12:54 am

Jim, thanks for sharing your dietary management of RLS and it's impact on liver. Can you share more info on what that low oxalate fiet is like?
Since you mention liver and according to other comments RLS shows a high correlation w Diabitus 2. I wonder if there is any relationship if RLS with hepetatis or patients who had hepatitis earlier in their lives.
I am brand new to this discussion group and very thankful to benefit from everyone’s wisdom!

Hi EVogel. notnowdad has lots more info in another Topic, which begins here: viewtopic.php?p=83780#p83780
There are links in that thread/Topic to other online resources.

Badnight - thanks for alerting me where to go. Have you tried that low oxalate diet?
It might be effective for some patients.

EVogel wrote: ↑

Sun Sep 05, 2021 4:44 am

Badnight - thanks for alerting me where to go. Have you tried that low oxalate diet?
It might be effective for some patients.

I haven't tried it yet. Every time I decide to, I back away again when I realize I'll have to stop eating a lot of the vegetables that I've come to believe I need. I should at least trial it for a couple of months. But I haven't had the energy to plan for it yet. I hope I don't regret the delay when I finally do try it.

badnights wrote: ↑

Tue Aug 24, 2021 7:32 am

An interesting model. What happens when we fast? Fasting would be similar to eating or producing oxalates with the iron, except worse, because there would be no iron available. So the WED/RLS would get worse the longer we fasted. Has anyone done a multi-day fast? Did your WED/RLS get better, worse, or no change?

I have fasted for up to 6 days, and my RLS got worse the longer I fasted. But then, the same is true if I lose weight fast (on ketogenic diet with time restricted eating), so I'm not sure it's the fasting.

I am trying the diet for the last 2 weeks with an increase in exercise with stretching and yoga! It seems to help a bit. How much not sure as it is difficult to quantify. But I am going to continue. I eat out a lot but can do well with an omelette as long as it does not have vegetables that are “oxalate offenders” and no bread or gluten. Lunch - can be fish or hamburger patty (no bread). Dinner - salads seem to work well. I do indulge on los fat ice cream. Keeping alcohol to a bare minimum. An occasional glass of wine! Give it a try and see if it works for you!

Ellie

notnowdad wrote: ↑

Wed Jul 14, 2021 1:46 pm

I have gotten almost complete relief from RLS by following a low oxalate diet. I have been reading some of the scientific studies and trying to come up with a possible explanation for what is happening in my body when I experience an episode of RLS. However, before I share my ideas I want to make clear that my version of a low oxalate diet includes avoiding glycine supplements, gelatin and gelatinous soups and stews because these foods stimulate my liver to produce oxalic acid endogenously.
[...]

Iron is typically bound to transferrin (the body’s distribution vehicle) with carbonate. However, oxalate can take the place of carbonate as the binding agent. Scientists have found that when oxalate takes the place of carbonate the bound iron is “locked up” so that it doesn’t release from the transferrin and, I assume, distribution is not accomplished.

Funny thing... When I read your post at first, it didn't sink in. But very recently I was in a conversation where this exact topic came up, and darn! that's an interesting thing. Apparently high oxalates can induce quite paradoxical situations, like low ferritin together with high transferrin values, and also the inability to increase ferritin via supplements. You might be on to something.

Also I'm starting to learn about a few more metabolic pathways... It seems that Glycine and related compounds (like Glycolate and Glyoxilate) are converted to oxalate if there is a functional vitamin B6 deficiency (https://pubmed.ncbi.nlm.nih.gov/12544342/). Even B6 supplements might not do the trick, as we need other vitamins like thiamin to convert B6 it to its active form. It might help to take P5P (pyridoxal-5-phosphate, the active form of vitamin B6), which is also available as a supplement, even though it's more expensive than normal vit b6 (pyridoxin hydrochloride). Also biotin seems to play a crucial role here. I'll let you know if I learn more about this.

Now this could explain why processed food is in general linked to high oxalates: Processed food is typically low in micronutrients. If vitamin deficiencies can lead to our body converting more glycin to oxalate, this might be the underlying mechanism.

EVogel wrote: ↑

Thu Sep 30, 2021 8:49 pm

I am trying the diet for the last 2 weeks with an increase in exercise with stretching and yoga! It seems to help a bit. How much not sure as it is difficult to quantify. But I am going to continue.

Sounds great! Keep in mind that oxalate detox can take years. And in some instances the body will produce too much oxalate on its own, see above...

I'm curious, does anyone here managing his oxalates is in the "Trying low oxalates" facebook group? I think it has very good resources for people who are scientifically interested in oxalates, many links to research articles and such.

(I'm not exactly a fan of facebook due to major privacy issues, and I'd strongly suggest to give FB as little information as possible. Personally I use a fake name and don't upload any private information. But as the number of resources for oxalates is rather limited I thought I'd share this.)

Not sure if we had this article in the discussion: "The Oxalate Effect on Release of Iron from Human Serum Transferrin Explained" (doi:10.1016/j.jmb.2004.03.049)

"The oxalate is able to bind to the iron in a symmetric bidentate fashion, which [...] makes iron displacement more difficult as documented by both iron release kinetic and equilibrium data.
[...]
Importantly, incorporation of oxalate as the synergistic anion appears to completely inhibit removal of iron from recombinant full-length hTF by HeLa S3 cells, strongly indicating that oxalate also replaces carbonate in the C-lobe to form a stable complex. "

Scanned the full paper, this caught my eye:
"A more quantitative approach is provided by kinetic analysis. Such studies reveal that the presence of the oxalate anion has a drastic effect on the rate of iron release at both at pH 7.4 and at pH 5.6 (Table 2). At pH 7.4 (the pH of the serum), iron release from the carbonate complex of hTF/2N is complete in 120 minutes. In contrast, removal of iron from the oxalate-bound hTF/2N under the stated conditions takes at least 5000 minutes. Similarly, at pH 5.6 (the putative pH of the endosome), iron release is much slower when oxalate serves as the synergistic anion. "

Very interesting.

Thanks for these thoughts and updates, Frunobulax!

A few research nuggets I found recently. Adding to this thread because I don't think we have another oxalate thread that collects the science.

https://pubmed.ncbi.nlm.nih.gov/22567004/, https://pubmed.ncbi.nlm.nih.gov/27844104/
If you're interested in oxalates and aren't afraid of a bit scientific lingo, check these out.

Cliff notes:

• Glyoxal is converted to glycolate and glyoxalate. Glycolate and glyoxalate are in balance (can be converted both ways). Glyoxalate is converted either to glycine (good) or oxalate (bad). (There are nice pictures in the publication but I can't post them here due to copyright issues.)
• Sources of glyoxal (and therefore oxalate) are, among others, polyunsaturated fatty acids (plentiful in western diet), vitamin C and glucose (!).
• Glyoxalate will be converted to glycine (harmless) using AGT (alanine:glyoxylate aminotransferase) using Alanine (an amino acid) and vitamin B6 https://en.wikipedia.org/wiki/Alanine%E ... ansaminase.
• Otherwise it will be converted to oxalate or or glycolate.
• Glycine can also be converted to glyoxalate. I couldn't figure out if we know when (or more precisely in which quantities) this happens, but it's suspected that deficiencies in vitamin B1, B6 and zinc will speed up glyoxalate generation.

So basically, if you want to reduce oxalate, you may want calcium and magnesium (both eliminate oxalate under certain conditions). If you want to prevent building up oxalates, you may want plenty of vitamins B1, B6, zinc and possibly the amino acid alanine (can be purchased as body builder supplement).
A ketogenic diet (no carbs) may or may not prevent oxalate buildup, we don't know how much glucose is converted to oxalate.

As a completely unrelated note, I started supplementing with alanine. (I'm already taking quite high doses of vitamin B1 and active B6, P5P.) Will report back in a few months.

Another paper:
https://www.sciencedirect.com/science/a ... 4721008330
High blood oxalate (low glycine/oxalate ratio) leads to mitochondrial dysfunction and atherosclerosis. Of course oxalate crosses the blood-brain-barrier, and mitochondrial dysfunction in the brain could basically cause any neurologic symptoms in the book...

As a completely unrelated note, I started supplementing with alanine. (I'm already taking quite high doses of vitamin B1 and active B6, P5P.) Will report back in a few months.

Looking fwd to this.

There was someone on here years ago who wrote that he successfully treated his WED with alanine & arginine. (specifically, his recipe was RapidDrive (brandname) Arginine 5000 and Beta-Alanine 3200, which are powders; 1/2 scoop of each (equal to 5g of the former and 2 g of the latter) mixed into water, drink in 5 minutes. My notes don't explain if you wait 5 minutes before drinking, or consume it all within 5 minutes. Probably neither matters.)

edited to fix typo July 2022