Folate receptor antibodies and cerebral folate deficiency

[MEkoan]

I googled hypersomnolence and cerebral folate deficiency = bingo.  I don't learn.  I really don't. 

Hypersomnolence is a nightmare, so to speak, isn't it.  It's a big feature of MS, too.  I don't nap if I can at all help it because it doesn't help, at all, and trying to pry myself out of the mini-coma is such a nightmare.

Anyway, google says: yes!  Interesting.

[Karin]

I had two little kids to watch and would just fall in and out of sleep sitting on a bench when I knew I shouldn't because I was watching them but couldn't help it. I would slap my face or bite my cheek. Then if I would get up from the bench I would see stars and need to drop on my knees or I would faint. Nice. Paradoxally I couldn't sleep well at night, go figure. My family doctor wanted to send me for a sleep study, he thought I must have had a sleep disorder. It is freaking expensive so I didn't do it. In addition I had no hope anything would be uncovered.

Then I started on Leucovorin and it all disappeared. Absolutely ZERO sleepiness during the day. NO dizziness. And I sleep at night now (not as well as I would like, but WAY better than before). Even if I have a bad night and sleep only 4-5 hours, I still feel rested (not as well as I'd like, but OK). Before, I would sleep 9 hours (not well), and still wake up so foggy.

I haven't tried ANY dairy since I started Leucovorin and I don't intend to. I am obsessive at reading labels, I just don't want to risk a flare of this cerebral folate defieincy. I had three since I started Leucovorin, and I don't know what triggered them, but that was scary enough.

[MEkoan]

I had two little kids to watch and would just fall in and out of sleep sitting on a bench when I knew I shouldn't because I was watching them but couldn't help it. I would slap my face or bite my cheek. Then if I would get up from the bench I would see stars and need to drop on my knees or I would faint. Nice. Paradoxally I couldn't sleep well at night, go figure. My family doctor wanted to send me for a sleep study, he thought I must have had a sleep disorder. It is freaking expensive so I didn't do it. In addition I had no hope anything would be uncovered.

Then I started on Leucovorin and it all disappeared. Absolutely ZERO sleepiness during the day. NO dizziness. And I sleep at night now (not as well as I would like, but WAY better than before). Even if I have a bad night and sleep only 4-5 hours, I still feel rested (not as well as I'd like, but OK). Before, I would sleep 9 hours (not well), and still wake up so foggy.

I haven't tried ANY dairy since I started Leucovorin and I don't intend to. I am obsessive at reading labels, I just don't want to risk a flare of this cerebral folate defieincy. I had three since I started Leucovorin, and I don't know what triggered them, but that was scary enough.

What you write is so familiar!  Well, except for the two little kids, they're yours.     But, I have succumbed to sleep on public benches on more than one continent and have watched people watch me struggle with irresistible sleep as though they thought I was drugged or drunk.  When I worked, I would often be unable to resist sleep at work -- certain activities which required still, seated attention were brutal.  I made documentaries and the hardest part was final edit which I directed but did not do hands on.  I had to sit still for hours overseeing and making decisions.  I could not stay awake or upright.  It was what you describe while watching your kids, almost exactly.

And, although I have suffered from hypersomnia all my life, I have also suffered from insomnia which is better now but the hypersomnia is much worse.  Part of the issue was that the hypersomnia was so much better (less intense) at night so I would sometimes want to stay awake to get things done that I could not do during the day.  For instance, I would do the part of the editing that I did myself - hands on - over night because that's when I could.   I had little understanding of why I did what I did the way I did which led to a whole lot of self blame and confusion.  I'm sure you can relate to that, too.

I think I have to find out about that test.  I find it easy to do things when I know why I'm doing them but I have a terrible time treating myself on spec. 

Thanks for alerting me to this possibility.  I'm very grateful.  I hope the MS community is hip to it.  I'm sure it all fits with Rich V's work which I can never understand because I'm so hypersomnolent!     Truth!

[Karin]

JustME I'll PM you the instructions. I have all the instructions needed for the test now, that you can bring to your doc. If anyone wants them, just PM me.

[MEkoan]

Many thanks, Karin!

[MEkoan]

I inadvertently did a little study with myself as sole subject.  Ice cream was on sale across the street and I bought a litre (because I just don't learn; also, more importantly, I don't remember!) and was unconscious for most of the couple of days I took to eat it.  Since I'm an idiot, I would eat some every time I woke because it was so easy, nutritious and there.  Then, it was gone and I went back to my usual diet which doesn't have a lot of dairy for ethical reasons and I could maintain wakefulness much better. 

Then, ice cream went on sale again!  I was fine the day I was eating it (yesterday - the whole thing, dark chocolate YUM) but then slept from last night until this evening in that horrible, groggy, drugged out of my mind state.  I had to get up several times to take care of my dog but would stagger through 5 to 10 minutes of dog care and then collapse into sleep again.  I still feel drugged.

It doesn't seem to hit right away.  As I was eating it, aside from the hair standing on end feeling that good chocolate icecream gives everyone (doesn't it?!), I was fine.  But, at 3 am I awoke with a sudden headache and a most bizarre drugged feeling.

I'm thinking, since I'm such an idiot, that maybe I should see if the test is available on insurance here, somehow... just to keep me in line, don't know.

And, I came back here to see what else you suggested, Karin.  Folinic Acid.  Now, I'm all confused re "folinic", "folic", "folate" but I'm hoping to come back tomorrow with a clearer mind.

How are you doing Karin?  Is it still working for you?  Are you still off dairy?  (If not for icecream and parmesian, I'd be off dairy, too ;o)

[Karin]

JustMe: try to remember this:

NO FOLIC ACID.

Folinic acid and/or methyl-folate both are good.

Another name for methyl-folate is 5-MTHF. GOOD.

That's because folic acid will bloc the folate receptors even more if your body isn't very efficient at processing it. That might mean removing wheat products since those are all fortified with folic acid, as well as multivitamin supplements including folic acid. A wheat-free and dairy-free diet can be very helpful anyways, I highly recommend trying this diet for anyone with chronic inflamatory health issues involving brain fog.

Concerning insurance, I am 100% sure your insurance won't cover that test, no point in even trying. It will cover it likely after it's commercialized, which i have no idea when it's going to be.

[Karin]

Here is an update:

I had been on 18 mg of folinic acid for a little over 9 months, which is the dose that seems to agree best with me. I have also been on a dairy-free diet for about 5 years, but in the past year I have scrutinized labels even more to make sure I don't get any milk products, not even milk fat (believe it or not, some 70% cocoa dark chocolate have milk-fat as ingredients, so watch out).

I've had ups and downs, but the main take away is that I have been completely off SSRIs for 9 months, and I have been able to exercise on a regular basis. I have not had irrestible sleepiness in the afternoons anymore, neither have I felt very heavy and very cold. So this is working for me long-term.

HOWEVER, something happened in the past two months, that could be a side effect of long-term use of leucovorin, though it could also just be a coincidence unrelated to leucovorin:

Two months ago I suddenly started having intense burning and tingling on my tongue, gums, palate and throat, as well as around my lips, as if I had just eating chili peppers or burned my mouth. Strangely, I couldn't see anything, no obvious redness, inflamation or sores. On and off, my lips would dry off and my mouth would feel very dry too. I went to my family doctor and my dentist, no one could figure out what the problem was. I was tested for food allergies, vitamin deficiencies, had head X-rays done, etc... nothing. I tried removing all my usual foods, no more toothpast, or lipsticks, or anything on my face, etc.. etc... nothing really helped. I tried several things, EFAs, flavnoids, antimicrobials, etc... some helped a bit.

Finally, at the suggestion of my family doctor, I tried stopping Leucovorin. He was wondering if this burning mouth syndrome could be a side effect of Leucovorin. I really didn't want to stop it, but after 6 weeks of burning mouth and no solution in sight, I was left no choice.

So what I did is stop Leucovorin (18 mg of folinic Rx), and replace it with 5 mg of L-5-MTHF (Thorne, OTC) and 3.2 mg of folinic acid (Kirkman brand, OTC). The following happened:

1. My burning mouth was much better within 2-3 days.
2. I did not have mood swings, drop in energy, sleep issues, or any stimulation from switching from 18 mg of leucovorin to 5 mg of L-5MTHF + 3.2 mg of folinic.

So now not only I am hopeful I solved my mouth problem, but I am also thinking this new smaller dose and different form of folate will work for me. I had already tried last year to replace 18 mg of leucovorin by 10 mg of L-5MTHF and it had been a disaster. Maybe 10 mg was too much and 5 mg will be the magic number for me. In any case, the lower the dose  I can function on, the better, I guess, side-effect-wise.

But we'll see how I do long-term on this. I'll update again in a few weeks.

[MEkoan]

Hi Karin,

I'm so sorry that you had to go through all of this!  You must have been quite dejected when it seemed as though you needed to stop a medication that had been so helpful.  But, it seems that this may be good news for you (touch wood!) after all!

Thank you so much for sharing this story here because it informs me as to how best to progress on my own trial.  I'm so grateful for all the detail you have provided in this post and your last to me.

I now have to home cook for my little dog with kidney problems which is a very complicated, expensive and time consuming exercise.  I thought, perhaps, I was just getting worn out by that but I was letting everything else drop away (EVERYTHING) so should not have been quite so wiped AND it was mostly hypersomnolence and not PEM which I found odd.  Well, since he started on his expensive diet (complete with CoEnzymeQ10 and other supps!) I have been eating bagels with peanut butter (bread, bread and more bread), spaghetti (bread) and jarred sauce and just to top everything off perfectly, I've been adding instant dark chocolate mix to my coffee every morning hoping for an added boost from the added caffein and chocolate but as you wrote, it contains milk!  So, I seem to be making a pretty good case for myself here.  Again today, I have slept pretty steadily until now, with occasional forays into the kitchen to prepare a meal for the dog and a quick stumble outside with him to pee... then I fall asleep again.  You really have outlined a very credible case for why this might be.

I always enjoy your posts, Karin, even when they don't benefit me quite so much but never more than today.  Oh, you also answered a question I did not have the wherewithal to ask and told me what it's called otc.  I was struggling to research that myself through the impenetrable fog to no good result.  So, thank you very much indeed!

I do hope you continue to have the good results you have!  If you had to go through the burning mouth trial, I sincerely hope it led to an even better regimen for you and I will be following your story most eagerly.  I don't know how many people on this forum have investigated this avenue but I really think any with hypersomnolence really should look into it.

I'm going to try to stagger to the local supplement shop to get my dogs Omega 3 tomorrow and will now know what to look for for myself.

Eyes crossed!

Big thanks!

(((you)))

[MEkoan]

So what I did is stop Leucovorin (18 mg of folinic Rx), and replace it with 5 mg of L-5-MTHF (Thorne, OTC) and 3.2 mg of folinic acid (Kirkman brand, OTC). The following happened:

If you have an opportunity, Karin, can you say why you are using both L-5-MTHF and folinic acid.

Again, thanks!

[Karin]

There isn't really a scientific reason why I am using both. But here are my thoughts:

1. I already know a low dose of folinic alone does not work for me: I need 18 mg to 25 mg a day. 12 mg is not enough (my sleepiness, fatigue and depression come back).

2. I already know that 10 mg of 5-MTHF alone (no folinic) did not work either: initially I got great results, but lots of extra stimulation (feeling plugged to a high voltage outlet for days, sleeping just a few hours at night, but feeling extra high and great), followed by a crash and weeks to recover.

So from the above I deduce I need less 5-MTHF, but maybe adding a bit of folinic in the mix would help 'even out' everything and prevent a crash. See, that's really not very scientific. I bought 5 mg 5-MTHF capsules and 800 mcg folinic capsules (folinic is not available in higher doses OTC), so a 5 mg dose of 5-MTHF and 4 capsules of folinic seemed like a do-able combo.

By the way, I found I really need to split the dose in two, morning and evening, because the half life of folate in the blood is a few hours. I avoid ups and downs this way So I sprinkle half the 5-MTHF capsule on my tongue in the morning, plus take two folinic capsules, and I take the remaining 5-MTHF in the evening plus two more folinic capsules.

Here is where I get them:

http://www.iherb.com/Kirkman-Labs-Folinic-Acid-800-mcg-180-Capsules/39004?at=0
http://www.iherb.com/Thorne-Research-5-MTHF-5-mg-60-Veggie-Caps/38045?at=0

You can also get those at this other store:

http://www.ourkidsasd.com/products/189%7CFolinic%20Acid%20800%20mcg.%20Hypoallergenic-Kirkman%20Labs
http://www.ourkidsasd.com/products/621%7C5-MTHF%20(5mg)-Thorne%20Research

[MEkoan]

FYI

No dairy yesterday, no dairy today and I've been awake since 9 a.m.!  I am also thinking just a little bit better.  Well, maybe not better but it is not quite so painful.  And, I did not have endless nightmares about being demented, or lost, or otherwise in the state I was in except the nightmare version.  Not a bad start!  (touch wood  )

I have not yet manage to get out for the 5-MTHF - which is what I'm going to try first - but no dairy may have already made a huge difference even though I'm still eating bread.  Interestingly, I had begun to crave bread at bedtime.  hmmmmm...

Anyway, enormous thanks to you, Karin, for your guidance in this most promising experiment.

[Karin]

FYI

No dairy yesterday, no dairy today and I've been awake since 9 a.m.!  I am also thinking just a little bit better.  Well, maybe not better but it is not quite so painful.  And, I did not have endless nightmares about being demented, or lost, or otherwise in the state I was in except the nightmare version.  Not a bad start!  (touch wood  )

I have not yet manage to get out for the 5-MTHF - which is what I'm going to try first - but no dairy may have already made a huge difference even though I'm still eating bread.  Interestingly, I had begun to crave bread at bedtime.  hmmmmm...

Anyway, enormous thanks to you, Karin, for your guidance in this most promising experiment.

Whoohoo!!!!! Excellent JustME!!! Keep it up and stick to the diet for a while. you're worth it!

I think it is a good idea to be dairy free for a while to let your (hypothetical) folate receptor antibody titers go down, and see how you adjust, then add the 5-MTHF. If that's your problem, then 5-MTHF should leave you awake and clear minded 20 hours a day at the beginning, at least it did so to me.

Also, if you feel really better for a few days, be on the look for short-lived mini crashes. I had those at the beginning. I think it was some adjustments from my brain levels of various stuff going up, maybe some detox, etc... That's why it will be good to go low and slow when starting 5-MTHF.

[MEkoan]

Whoohoo!!!!! Excellent JustME!!! Keep it up and stick to the diet for a while. you're worth it!

I think it is a good idea to be dairy free for a while to let your (hypothetical) folate receptor antibody titers go down, and see how you adjust, then add the 5-MTHF. If that's your problem, then 5-MTHF should leave you awake and clear minded 20 hours a day at the beginning, at least it did so to me.

Also, if you feel really better for a few days, be on the look for short-lived mini crashes. I had those at the beginning. I think it was some adjustments from my brain levels of various stuff going up, maybe some detox, etc... That's why it will be good to go low and slow when starting 5-MTHF.

It's so wonderful to be able to maintain wakefulness!  It's so amazing not to be living in that nether world of sleep or near sleep.  It's been plaguing me for quite some time now, and has been an issue since the beginning of my illness - or longer, actually - and the severity of the state could well coincide with times of more or less (some or no) dairy.  There have been times when I have had little to none which may coincide with better health, don't know but I'm very curious now!  Very!

I would expect mini-crashes if I feel better.  I would also expect to be able to push myself to PEM which I do not experience during the mini-coma state the most hideous aspect of which is that it is not only non-restorative, it's exhausting.  I would try to tell myself, as I was being dragged back into it, that the sleep would be good for me but it's like being drugged, it's not good for you, it's like having anesthesia.  I hate it!

I am very, very grateful to you!  If not for you, I would have had no idea where to go or what to consider this time.  I would be rolling over and ordering pizza just to keep myself alive.  (Pizza, too, has featured in this fiasco.)  I would not have considered this state could possibly have been related in any way to dairy.

Thank you, thank you, thank you!

[MEkoan]

Karin,

I thought I would pass along to you a little treat that is both dairy and gluten free.  I can't stand the thought of you having nothing yummy or chocolate   

I don't know whether or not you like coconut but I think Streit's Coconut Macaroons (Kosher for Passover - no dairy; also no gluten) are absolutely delicious!   

All the best to you!