What is Going on?? Neurotransmitters? Overmethylation? ANY IDEAS??

[Kimsie]

It is true that B6, particularly if it isn't taken with enough of the other B's, can cause these types of neurological symptoms. But the recommendation to limit the dose to 100 mg per day seems excessively cautious to me. If you take a look at the cases where this has happened, some elderly people took 600 mg a day for well over a year before symptoms started and didn't stop taking it when the symptoms started. There were some other cases also with higher doses, up in the grams, and maybe some with a little lower doses. But no one got these symptoms taking 600 mg orally for a month or two, which a person could do as a test to see if it would help them. Unfortunately, when they report on these cases, they never say what, or how much of the other B vitamins the person was taking.

We are using 600 mg a day of the P5P form, which has 400 mg of B6 in it, and we use high doses of all the other B vitamins along with it. The orthomolecular doctors have given doses as high as 3 grams a day (of regular B6) without problems, but they always give high doses of the other B's with it.

My son with schizophrenia HAS to have larger doses of B6 than 100 mg. If he does, he can be off medication and be pretty much symptom free, (he takes a lot of the other B's, too, he needs a lot of niacin and folate). This is really important because the medication has bad side effects and doesn't take away all of his symptoms. I mistakenly thought that he didn't need as much B6 last spring and I told him to take less and he had a terrible relapse that started a few weeks after he lowered his dose of P5P to 100 mg a day, even though he didn't change the other supplements.

 

[Johnmac]

I have one son who was fatigued for over a year after having had mono. When he started taking methylfolate 5 mg a day his fatigue went away. After a few months on the methylfolate, he became very depressed. I think I have figured out why and the short answer is that because of my experience with my son I would think that you probably need to take a lot of B6 in the form of P5P, 50-100mg 3 times a day until your dreams become too vivid and then cut back. Niacinamide 500 mg should help a lot with the anxiety right away.

I've read Hoffer's stuff on niacinimide/B3 and like the idea of it.

One is also meant to take it in decent quantities for pyroluria (which I suspect I have).

However Fred says to limit it to pretty low amounts, doesn't he?

Anyone managed to resolve this paradox?

 

[Kimsie]

Have you tested low in zinc? (Zinc is low in pyloruria.) The son that I was talking about in your quote tested very low last winter and if he doesn't have nearly 50 mg of zinc a day he gets signs of food reactions. Our other son doesn't have any problem with zinc levels, but he still has to have a lot of B6.

I want to note again here that none of us in our family has CFS or ME, so our experience may not parallel people who have them. I post here because 1. I have gotten a lot of information here that has helped me. and 2. I think that some of the things I learn might help some other people here. There is a lot of overlap with quite a few chronic illnesses, in my opinion.

I found one quote from Freddd (this is the first time I have heard of Freddd) which says that he feels that niacinamide in doses over 100 mg can cause a paradoxical folate deficiency. I am not sure what the paradoxical part means, but in our treatment protocol for our sons who have schizophrenia and depression we have found that we do have to use large doses of folate but we think it is the B6 that makes so much folate needed because 1. folate and B6 are used together in the SHMT reaction and 2. when we purposely increased the B6 (P5P) to 600 mg a day (my son with schizophrenia had done it by accident when we first stumbled on to the combination of supplements that worked for him) different people got symptoms of fatigue (already known to be caused by low folate in our son with depression) anxiety (in our son with schizophrenia, SAMe is needed to degrade epinephrine) and headache (in everyone, we don't know why), and everyone had their symptoms go away with a higher dose of folate. But less folate was needed after a few days when the enzymes adjusted, but still a large amount.

That said, niacin is used in so many reactions that it seems probable to me that it could accentuate folate problems in some people - I think it just depends on where your genetic weaknesses are.

If you have pyloruria you will want to take large doses of B6 and you will also need zinc and niacinamide. In our experience, you will need a lot of folate, too, and we find it all works better with a largish dose of B1, B5 and a not quite so large dose of B3. If you take high doses of one you need to balance it out with the other B's. I think the B12 is pretty individual, but we take some of that just to be on the safe side.

So I think the answer to the paradox might be that you have to experiment and see what works for you, but if you take a lot of B6 and niacinamide, be sure to balance it out with the other B's and you should stay out of trouble. I think that Freddd's warning was about what can happen if you take a lot of one B without enough of another one.

 

[Critterina]

It is true that B6, particularly if it isn't taken with enough of the other B's, can cause these types of neurological symptoms. But the recommendation to limit the dose to 100 mg per day seems excessively cautious to me.

Kimsie,

I totally respect and am in awe of what you are doing with your kids. I don't mean to suggest that YOU do anything different.

My concern is for others reading these posts, some with significant brain fog, who are trying to patch together something that will work for them, sometimes without the support of medical professionals (and I don't mean for lack of trying). When someone recommends something that has been toxic for others, I just feel it should come with a note. We all know that one person's cure is another's poison - at least if we read this forum we do.

Do you have more than anecdotal evidence that higher B6 is safer when taken with higher amounts of other B vitamins, and which ones? Thanks.

Critterina

 

[Kimsie]

Yes, care needs to be taken. I don't in the least mind your pointing out what you did. I was just pointing out the other side.

It doesn't seem likely to me that anyone would fund a study comparing the effects of taking B6 with and without the other B vitamins so it is all anecdotal evidence. Here is a report on studies involving B6 and whether they caused neurological problems or not. Unfortunately very few of the studies mentioned say anything about whether or not other B vitamins were taken, and when they do they are mostly not specific about which ones and how much of each.

 

[Johnmac]

Sorry for late reply - country-hopping.

No, haven't tested low in zinc. I just suspect I may have pyroluria as the symptoms are a good fit. In the wilds of SE Asia presently, so can't do the test right now anyway. I'm on 200mg/day of zinc presently on the precautionary principle - and 400mg of B6.

I don't have ME/CFS either. What fatigue I had vanished when I began the Freddd protocol. I appreciate your posting here, as people with/without ME can learn from each other because of the overlaps. I do have a daughter with delusional stuff happening.

I'm not too clear on the mB12/m-folate relationship, only that I think I might need more of the former. Get very wired & anxious otherwise (tho too much LCF is the worst offender in this area).

Your report about your sons makes me wonder if I need to raise the folate quite a bit. I get huge anxiety; I guess it's possible the B6 & folate could be doing that, now I have raised the B6 dose. I always wanted to explore the theory that my crashes were caused by paradoxical folate deficiency anyway (tho I get very few of the symptoms Freddd lists for that).

Niacinimide is the question. Freddd says to take little; but it is important in pyroluria. The difficulty with experimenting is that there are so many variables to test. But it has to be done. But I'll balance the B3 out with other Bs as you suggest.

Thanks for the ideas...

Have you tested low in zinc? (Zinc is low in pyloruria.) The son that I was talking about in your quote tested very low last winter and if he doesn't have nearly 50 mg of zinc a day he gets signs of food reactions. Our other son doesn't have any problem with zinc levels, but he still has to have a lot of B6.

I want to note again here that none of us in our family has CFS or ME, so our experience may not parallel people who have them. I post here because 1. I have gotten a lot of information here that has helped me. and 2. I think that some of the things I learn might help some other people here. There is a lot of overlap with quite a few chronic illnesses, in my opinion.

I found one quote from Freddd (this is the first time I have heard of Freddd) which says that he feels that niacinamide in doses over 100 mg can cause a paradoxical folate deficiency. I am not sure what the paradoxical part means, but in our treatment protocol for our sons who have schizophrenia and depression we have found that we do have to use large doses of folate but we think it is the B6 that makes so much folate needed because 1. folate and B6 are used together in the SHMT reaction and 2. when we purposely increased the B6 (P5P) to 600 mg a day (my son with schizophrenia had done it by accident when we first stumbled on to the combination of supplements that worked for him) different people got symptoms of fatigue (already known to be caused by low folate in our son with depression) anxiety (in our son with schizophrenia, SAMe is needed to degrade epinephrine) and headache (in everyone, we don't know why), and everyone had their symptoms go away with a higher dose of folate. But less folate was needed after a few days when the enzymes adjusted, but still a large amount.

That said, niacin is used in so many reactions that it seems probable to me that it could accentuate folate problems in some people - I think it just depends on where your genetic weaknesses are.

If you have pyloruria you will want to take large doses of B6 and you will also need zinc and niacinamide. In our experience, you will need a lot of folate, too, and we find it all works better with a largish dose of B1, B5 and a not quite so large dose of B3. If you take high doses of one you need to balance it out with the other B's. I think the B12 is pretty individual, but we take some of that just to be on the safe side.

So I think the answer to the paradox might be that you have to experiment and see what works for you, but if you take a lot of B6 and niacinamide, be sure to balance it out with the other B's and you should stay out of trouble. I think that Freddd's warning was about what can happen if you take a lot of one B without enough of another one.

 

[Kimsie]

I would just add a couple of things. We have just realized in the past couple of days that it is a good idea to take about 2 times as much magnesium as P5P. We are finding that it works better that way. It has to do with sulfation. You might already be taking magnesium. We are finding that with more magnesium, less B6 is needed, right now we are taking 300 mg of P5P and 600 mg of Mag, total, divided in three doses. You don't need as much P5P as regular B6. If you are taking regular B6, you might want to change to the P5P form, because it is the active form. I like to use the uncoated kind, it works just fine. If I get some with a coating on it I cut it to expose the inside because it doesn't really need to be coated and you can't always be sure that the coating dissolves.

You might need more folate if you feel anxious, or you might need more niacin or niacinamide, or you might need more of both. If you were not anxious before you started the high B6 then it is probably folate or it could be that you need more magnesium.

Is your daughter actually delusional? How old is she? We have a lot of experience in this area, because of my son's schizophrenia. When we were using this protocol before, and my son with schizophrenia was doing so well, and then I told him that I thought he didn't need so much B6, he became very delusional (and he was hearing voices and conversing with them) after about a month at the lower dose of B6, even though all the other supplements were the same, including high magnesium. If you would like to talk with me about your daughter, why don't you PM me because a discussion on psychosis might be somewhat out of place here.

 

[Gondwanaland]

I would just add a couple of things. We have just realized in the past couple of days that it is a good idea to take about 2 times as much magnesium as P5P. We are finding that it works better that way. It has to do with sulfation. You might already be taking magnesium. We are finding that with more magnesium, less B6 is needed, right now we are taking 300 mg of P5P and 600 mg of Mag, total, divided in three doses.

I am glad to read that. It is my understanding that one of the main activities of B6 is to improve Mg absorption and metabolism. You might find of interest a letter published long ago in "The Lancet" that I posted here. Magnesium is vital for sulfation, glucuronidation and methylation directly, and indirectly to glutathione conjugation, acetylation and glycination. So, whaterver which one of the detox pathways you choose to focus the treatment, don't skimp the Mg.

I just wish it was this "easy"... Of course one must pay attention to further imbalances with calcium and potassium for instance, and be sure the patient is able to handle the detoxing side effects (I believe Mg also helps to cope with the re-toxing provoked by the detox).

 

[Kimsie]

Thank you so much for the link to that letter.

Now I understand why at first the high B6 was working so well and after a few days it wasn't working as well. P5P (without sufficient magnesium) inhibits sulfotransferase, and allows phenols to accumulate. Then when the phenol levels are high they inhibit aminolaevulinic acid dehydratase, which is the second step in heme synthesis, and they inhibit alpha-ketoglutarate, which we are already trying to uninhibit because we need it to make succinyl-CoA - these are two things in the pathway to make heme and catalase, which we need in order for dopamine beta hydroxlase to change dopamine to norepinephrine, and to get rid of H2O2. So the P5P we need for heme synthesis was actually causing heme synthesis to be inhibited in a different way, until we added enough magnesium!

I think we may be able to lower the B6 dose a little more, but I already know that 100 mg of P5P isn't enough, because we tried that before with high mag and S had a relapse. I am hoping that we can get it down to 200 mg a day, and not need so much magnesium. We are flirting with bowel tolerance right now. Eventually we should be able to figure out the lowest effective doses of everything.

 

[Gondwanaland]

@Kimsie take a look at this discussion about how salicylates inhibit EFAs metabolism and hormone production. I was able to reverse salicylate sensitivity with magnesium supplementation only. Everything worked better for me after that (far from being happy yet though).

I think it could be of great benefit to analyze SNPs under the standpoint of one's ability to keep/absorb minerals and vitamins. But perhaps it is epigenetic and resides in the gut flora...

 

[Kimsie]

I will take a look at it, but I don't think we are having a problem with salicylate sensitivity, at least not my two sons. They were taking high doses of magnesium, and even having magnesium IV's with up to 800 mg of elemental magnesium and they tested normal two times for RBC magnesium and never low. And at that time they were only taking 50-100 mg of P5P a day, and they were still having symptoms. S even had a terrible relapse on that lower dose of B6 with very high mag, when he had been symptom free with higher B6 and the same amount of mag (and no medication).

It seems to be the high dose of B6 that makes them need extra magnesium (they were generally taking 300 mg of mag anyway). S has tested low in B6 but D has never been tested. However, next month I am planning to have them tested on all the main vitamins, and the complete RBC mineral test again, to make sure that our protocol isn't getting anything out of balance.

Although there may be a genetic component to the way S and D absorb from their gut, they were each normal until they had mononucleosis (6 years apart). It is my belief that the oxidative stress from the mono started a vicious cycle, and that vicious cycle is the cause of their problems. Their individual genetic weaknesses are the pathways where the symptoms show up and in that sense their problems are genetic, but without the vicious cycle (of high sulfite and oxidative stress) they would become normal again, and not need to take vitamins, etc. If a person has been ill since they were born then it may be completely genetic. I have tried analyzing so many genetic snps and pathways, but it really hasn't been any help, except for that it made me study the pathways and try my best to learn to know and understand them, and understanding the pathways is a great help.

 

[Johnmac]

I would just add a couple of things. We have just realized in the past couple of days that it is a good idea to take about 2 times as much magnesium as P5P. We are finding that it works better that way. It has to do with sulfation. You might already be taking magnesium. We are finding that with more magnesium, less B6 is needed, right now we are taking 300 mg of P5P and 600 mg of Mag, total, divided in three doses. You don't need as much P5P as regular B6. If you are taking regular B6, you might want to change to the P5P form, because it is the active form. I like to use the uncoated kind, it works just fine. If I get some with a coating on it I cut it to expose the inside because it doesn't really need to be coated and you can't always be sure that the coating dissolves.

You might need more folate if you feel anxious, or you might need more niacin or niacinamide, or you might need more of both. If you were not anxious before you started the high B6 then it is probably folate or it could be that you need more magnesium.

Is your daughter actually delusional? How old is she? We have a lot of experience in this area, because of my son's schizophrenia. When we were using this protocol before, and my son with schizophrenia was doing so well, and then I told him that I thought he didn't need so much B6, he became very delusional (and he was hearing voices and conversing with them) after about a month at the lower dose of B6, even though all the other supplements were the same, including high magnesium. If you would like to talk with me about your daughter, why don't you PM me because a discussion on psychosis might be somewhat out of place here.

Hi Kimsie,

Thanks for your interest in my hopefully transient anxiety problem.

It's still present after 3 weeks, and clearly biochemical: after your suggestion I tried 800mg of m-folate under my tongue for 1.5 hours (probably 6 times my normal dose): it had a small (20%) effect for a while - lasted an hour or less.

I stopped taking oral Mg as it upset my stomach too much. I now use Epsom salts. No baths in SE Asia where I am now, so I am sponging myself with Epsom salts & leaving it on my skin all day. But again no effect on the anxiety.

I can't get my hands on niacin at present: will try it when I get home. However I am eating a ton of chicken and fish: wouldn't they be providing me with enough?

So I'm at a loss. The anxiety began when I upped my L-carnitine fumerate too much. That's happened before, and usually I just take less and the anxiety goes away. But not this time.

I often wake feeling okay, then the anxiety builds through the morning - peaking around lunchtime. By evening it's usually 80% gone. Occasionally during the day it's decayed into depression.

5HTP, phenylalanine, tyrosine & GABA have had some effect - up to 20% at times, but sometimes nothing. It's as if they were struggling against a deficiency.

So my first guess is that the Freddd protocol (mB12, m-folate, LCF & adenosyl cobalamin) has brought about a nutrient deficiency of some sort. But I don't know what. I eat a ton of yogurt I culture myself, so riboflavin & calcium should hopefully be covered without the need for supps.

The other guess is that I have pyroluria, as the raised doses of B6 & zinc seemed to help in a trial or two.

Okay, I'll PM you so we can talk about the joys of psychosis.

Thanks again...

 

[AndyPandy]

Toxicity from B6 may show up in numbness and pain in your extremites. Most practitioners recommend not to exceed 100 mg/day. Just sayin'.

I have just received my B6 test results.

713 (range is 35 to 110)

I have long term peripheral neuropathy with numbness and tingling. Skinny type 2 diabetic.

I have been taking 8mg a day B6 via a multivitamin and 25mg a day via a B complex. That's only 33mg a day.

I don't tolerate meds well and only need small amounts. Seems I need to be careful with supplements as well.

I will be stopping the supplements and talking to my CFS/ME specialist next week.

Best wishes Andy

 

[Critterina]

I have just received my B6 test results.

713 (range is 35 to 110)

I have long term peripheral neuropathy with numbness and tingling. Skinny type 2 diabetic.

I have been taking 8mg a day B6 via a multivitamin and 25mg a day via a B complex. That's only 33mg a day.

I don't tolerate meds well and only need small amounts. Seems I need to be careful with supplements as well.

I will be stopping the supplements and talking to my CFS/ME specialist next week.

Best wishes Andy

Well, best wishes to you, AndyPandy!
Something else is going on there and I'm glad that you will be seeing a specialist. How could your B6 have got so high? Please let us know what you find out. And maybe check your diet against these foods high in B6: http://www.healthaliciousness.com/articles/foods-high-in-vitamin-B6.php

 

[AndyPandy]

Thanks @Critterina. I had a look at that list and nothing leaps out at me. I think @PennyIA had a similar problem in the past which improved with methylation. I am about to start methylation and hope I can tolerate it.

 

[Critterina]

Thanks @Critterina. I had a look at that list and nothing leaps out at me. I think @PennyIA had a similar problem in the past which improved with methylation. I am about to start methylation and hope I can tolerate it.

I really have no idea how methylation would bring down your B6 - but maybe that's because I really don't know how B6 works in anything, just that it does. That would be interesting to figure out. I'm sure you've read Caledonia's document about starting low and going slow, but if not, please do. Tolerance is sometimes in the dose.

 

[Valentijn]

@AndyPandy - Do your results specify a type of B6?

 

[AndyPandy]

@Valentijn

The test results say this:
"For information: Pyridoxal-5-phosphate is the active co-enzyme and its measurement has found to be adequate for the assessment of Vitamin B6 status"

I have been supplementing with Pyridoxine Hydrochloride.

I have posted some further details on the thread "Methylation Cycle and Vitamins ???"

Thanks for your interest.

 

[PennyIA]

Thanks @Critterina. I had a look at that list and nothing leaps out at me. I think @PennyIA had a similar problem in the past which improved with methylation. I am about to start methylation and hope I can tolerate it.

I did have a similar problem. Cutting back on the artificial form of B6 allowed my numbers to drop but did not improve my symptoms. Per the doctors there was NOTHING in my diet, nor taking the B6 could POSSIBLY ever cause such high b6 levels. My mother ALSO got told the same thing (which btw is how I finally managed to convince them to test my b6 levels). I'm assuming it's something genetic that basically kept the b6 in our system instead of allowing us to process it and/or eliminate it. Not bringing it in, was the key to getting normal b6 test levels. Of course, I can only guess at what's truly happening... but if our methylation process improves with treatment it might have been enough to get over some kind of hurdle and allow my body to process better and heal.

I had peripheral nueropathy on right side of my body (tingling, numbness, a 'limitation on sensitivity') - this meant that while I could feel touch and sensation, it felt weaker almost like it was trying to get through a thick coat of something prickly. My most hated side effect of this was that no matter what I did, the right side was always colder than the left side. Try explaining why you are wearing a tank top on the left side and a long sleeved shirt and sweater on your right side. .. (besides looking silly)... or why you had to keep messing with the shower temperature throughout the entire shower because in order for the right side to feel comfortable, the left side would turn pink... note- the right side would NOT turn pink, it didn't sense the heat at a physical level. Drove me NUTS that they were telling me this was all in my head. But they didn't want to talk about b6 toxicity with me because that might make me even more of a hypochondriac. They wanted to minimize all lab findings.

P5P has been part of my methylation treatments.

FWIW - I seem to respond well in other ways to the methylation treatment; for at least periods of time. I am still tweaking my treatment to see if it will work for longer periods of time and this time around, I'm taking a week off of all supplements every month to see if it will let me tolerate it longer while we still figure out what combination of what will work best for me.

 

[AndyPandy]

@PennyIA thank you so much for responding.

Strangely, I too have neuropathy only on my right side. Numbness and tingling in toes, foot and fingers, but not temperature differences compared to the left side. Poor you, that must have felt awfully uncomfortable.

I have a few questions and I would be grateful for your answers. You are the only other person I have found on PR with this problem

Has your neuropathy improved? If so, what do you think might have helped?

Did you start methylation after your B6 levels dropped? How long did it take for your B6 levels to come within range?

How much P5P are you taking as part of your methylation treatments?

Like you, I suspect this may be yet another genetic problem!

Best wishes Andy