• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

Folate Issues & Methylation

topaz

Senior Member
Messages
149
Um, I dont know if it's a downside exactly, but low folate is anti-cancer. That does not mean high folate is pro-cancer. It just means that cancer needs folate to divide and grow just like regular cells, so a folate DEFICIENCY (which may make you feel like crap) will also prevent cancer. [/url]


Rydra

Rydra

I am at a disadvantage here as I dont have links to support what I am saying but prior to starting methylation I extensively researched folate and came across a number of reputable sources (include some peer reviewed ones) that support the theory that folate does support SOME cancers - prostate and bowel being two that I recall but there were a few more, not many however. The articles were clear that it only applied to some forms of cancer AND THAT these studies were done with folic acid and NOT folinic or 5 MTHF and clearly stated that final conclusions could not be drawn, especially in regard to the form of folate.

Remember that folate is readily given to women who have trouble carrying a pregnancy full term due to miscarriages and test positive for the MTHFR gene. While this practice is less than a decade old, no reports or trends have emerged (yet) that these women develop breast, or other, cancer. Ditto for the children that were subject to a relatively speaking high folate pregnancy (although is it high if large supplements compensate for an initial shortfall??)

Note that the conclusions about folic acid and cancer were based on studies of those who already had the cancer, not that it causes cancer. And the folate form used was folic acid.

Best
 

maddietod

Senior Member
Messages
2,859
Hi Madie,

You just barely begin to look like you are homing in on a state of healing and insteado of letting thinbgs stabilize and home in on healing you are running full speed away from healing now. Why are you doing this? It doesn't seem to make any rhyme or reasom.

Hi, Freddd,

Thanks for chiming in. I admit that I don't know what I'm doing, and sometimes my brain gets "great ideas" that confuse even me, later. But I stopped the solgar and potassium by mistake - I just forgot to take them most of one day. So the next day it occurred to me to test the paradoxical folate deficiency idea by returning to the low carb, high vegetable and protein diet that works best for me, without taking metafolin. I felt great after eating a salad for lunch and broccoli for dinner.

I think that with the mb12 on board, my body can process folinic acid.

Then I got curious about how much metafolin is needed your protocol in the absence of this paradoxical deficiency. Because I hadn't been looking for that information, previously. So I'm still wondering about that.

My potassium meter just arrived, and I'll be keeping right on top of that. After reading snow athlete's thread, I've put potassium in my car and in my purse, as well as right beside my bed with water.

As always, thanks.

Madie
 

Dreambirdie

work in progress
Messages
5,569
Location
N. California
This morning I became very ill from too much potassium (K). I had taken 3 tablets of K Citrate (99 mg/each) before bed, and had taken about 500 mg total during the day yesterday, prior to that last dose. I woke up this a.m. with profuse sweating, severe nausea, diarrhea and heart palpitations.

I have been drinking coconut water (690 mg K) 2 times a day for about a year and sometimes taking 4 packs of Emergen-C (which has 200 mg K/per pack) in addition, and never had any problems with that, with K in a food source. When I switched to the supps for convenience sake, it ended up making me sick.

I just wanted to post this, so others are made aware that sometimes not just the amount but also THE SOURCE of the K is an important thing to consider. In my case it was HUGELY important, and today I am paying the price for thinking potassium == potassium.

Also, I think I am hundreds of times more sensitive than most of the people on this thread, because you all can take 100s of milligrams more of these supps without a significant problems, and I just cannot do that.

I am going to stick with what I know works, and not experiment anymore. I don't want to cause another long crash. :In bed:
 

maddietod

Senior Member
Messages
2,859
Hi, Dreambirdie,

I'm sorry you had such a rough time with the potassium. I've tried a few different kinds, testing out the dosage carefully, and I don't have any problems. Which is lucky, because old potassium tests I found recently showed me very low "normal." Here, that's considered deficient, and is especially dangerous for people on the active protocol.

I agree that it's important to test all supplements carefully, especially for people who have a history of reactivity. I haven't emphasized that in this thread, because I'm not particularly sensitive in that way. Even so, I add new things one at a time so I can tell what's doing what.

I hope you're better now.
 

Dreambirdie

work in progress
Messages
5,569
Location
N. California
Hi, Dreambirdie,

I'm sorry you had such a rough time with the potassium. I've tried a few different kinds, testing out the dosage carefully, and I don't have any problems.

I hope you're better now.

Hi Madie--

Thanks for your concern. I am not in a crisis anymore, as I was this a.m., but I am not really "better" yet. It's been a day in bed, drinking lots of water and taking no supps of any kind.

As I have already mentioned, I have used K before (up to 1200 mg/day), but this particular brand of K (Jarrow Potassium Citrate) really reeked havoc on my body. I don't know why, but I do know I am not going to take it anymore.
 

rydra_wong

Guest
Messages
514
This is also useful because it tells me that I can't figure out how much methylfolate I should be taking from symptoms. I wouldn't know if I'm depleting.

This is a concern now that I'm rethinking my supplements. After a week on 250mcg mb12, I stopped taking metafolin (other than 400mcg in one B-Complex). I immediately stopped getting low potassium symptoms. I went back to my low carb, protein and vegetables diet, and am feeling no worse than before this switch. Plus I'm getting bursts of energy (raking leaves). [I'm not drawing any conclusions from this - it's too soon and too complicated.]

If I go by the SMP ratio, for 2000mcg hb12 I was taking 500mcg folates and eating a lot of vegetables. So I'm in the ballpark. Is there any downside, short or long term, to supplementing with too much methylfolate?

For what it's worth - I also experience unstable potassium at high mfolate. I have no loss of function that I am trying to recoup and dont like that unstable potassium level symptom. I am hypothyroid right now so I am pursuing fixing that...I am just listening to everyone trying things with folate, but not so anxious to jump on board myself while there are other things that need sorting out...I do have perfect homocysteine with only 2 Thorne Basic B's, 1 800mcg mfolate, 2g TMG, and 50mg P5P, so it's not so clear cut that more mfolate is better.

Rydra
 

soulfeast

Senior Member
Messages
420
Location
Virginia, US
Dysautonomia:

http://dinet.org/

That is very interesting about the cholenergic containting polyphenols.. I have OLE on hand.. I am going to try that.. that would be wonderful!!!! This adrenaline is driving me insane. I had no clue about the connection to breast cancer reduction either which is an issue for COMT++ folks..

I dont know the chemistry as to what makes adrenaline and dopamine .. would need to read up.. but I also have tested strangely low at times for the catcholamines as in right before I started freddd like doses.. very strange. but I also testd low in tyrosine which I do think is a precurer and Rich wil have to speak to this, but I think he mentioned tyrosine being low as an issue with not methylating properly?

Maybe and out on a limb why I have heard another MD say that adrenaline is actually low when you are not methylating. ??? So an uptick in adrenaline could be s sign you are methylating.. which would validate freddd but also still yasko..??

Soulfest, This sounds interesting to me. I also have two COMT defects, one +/+ and one +/-, however on two neurological tests 1-2 years apart I always tested low dopamine and low serotonin and low epinephrine (well I failed 11 out of the 13 neurological tests and the low epinephrin was a - duh! - because I have severe allergies). As far as I know I have no catecholamine surges (that refers to stuff made from dopamine, right?) but the thing is that I have 18 genetic defects out of 30 and I ahve had neurological problems my whole life so idk if I can separate one thing out from another. It was only by reading WrongDIagnosis that I found I had many symptoms I ignored in common with others - things like feelings of insects crawling on me - weird stuff.
(I should tell you I have 3 genes causing low BH4 which seems to trump the two COMTs).

If you wouldn't mind I'd like to hear a bit more - but remember I dont know a lot of these terms...like what is dysautonia? I am starting to think I have dopamine responsive dystonia - which is like a diurnal ataxia - like you move a little jerkily instead of smoothly. Is that the same as dysautonia?

I have never had red urine from mB12 but I only took 5 pills one time and since it did nothing for me I did not pursue it. I am adverse to using up my supplement bottles in one day... I could not possibly afford that. I am fairly certain that the high mfolate dose is what I really should be taking but I cant - same reason, so I take 1/day and I think over time I am ok on that. Maybe could be a bit better, but unless I go one deplin it's not gonna happen.

Here is something strange - I get a feeling like Vicks Vaporub - like extra wonderful perfusion in my brain if I take a high dose of choline, or a high dose of omega-3 or from a deplin-sized dose of mfolate. I have been afraid that by ignoring this (not taking deplin for example) that maybe it means my homocysteine behind the BBB is really high (even though it is not high in the rest of me). But now I am starting to wonder if these substances are cholinergic. For instance mfolate raises BH4 which raises dopamine. I think maybe choline raises dopamine? Well anyway surealy raises acetylcholine (is this cholinergic?) I know so little about this, but it seems I have to educate myself or I never get anywhere. Did you sister say what things you should avoid because they are cholinergic?

Can you take me through cholinergic dumping symptom by symptom so I could recognise it? I am just a jumble of symptoms - my normal is probably actually weird - you know? For instance, would you think getting jitters from caffeine consumption icould be cholinergic dumping, or just normal? I have super caffeine jitters just now and suddenly wondered how many things I ignore as 'just me' are actually symptoms of something I could avoid.

Oh, btw, I take 1g/day of olive leaf extract high inh oleuropein polyphenol and now they are saying that cholinergic-containing polyphenols use up COMT in +/+ and +/- genotypes and result in 40-60% less chance of breast cancer. I am wondering if the reason I am not sensitive to methyls is because the oleuropein is sponging them up!
http://cancerres.aacrjournals.org/content/63/21/7526.full

Thanks for any info. Very interesting.
Rydra
 

soulfeast

Senior Member
Messages
420
Location
Virginia, US
the dumping feels like I am being "fed" IV caffiene.. climb the walls, can't sleep, wired energy..

Dysautonomia:

http://dinet.org/

That is very interesting about the cholenergic containting polyphenols.. I have OLE on hand.. I am going to try that.. that would be wonderful!!!! This adrenaline is driving me insane. I had no clue about the connection to breast cancer reduction either which is an issue for COMT++ folks..

I dont know the chemistry as to what makes adrenaline and dopamine .. would need to read up.. but I also have tested strangely low at times for the catcholamines as in right before I started freddd like doses.. very strange. but I also testd low in tyrosine which I do think is a precurer and Rich wil have to speak to this, but I think he mentioned tyrosine being low as an issue with not methylating properly?

Maybe and out on a limb why I have heard another MD say that adrenaline is actually low when you are not methylating. ??? So an uptick in adrenaline could be s sign you are methylating.. which would validate freddd but also still yasko..??
 

maddietod

Senior Member
Messages
2,859
Dysautonomia:

http://dinet.org/

That is very interesting about the cholenergic containting polyphenols.. I have OLE on hand.. I am going to try that.. that would be wonderful!!!! This adrenaline is driving me insane. I had no clue about the connection to breast cancer reduction either which is an issue for COMT++ folks..

I dont know the chemistry as to what makes adrenaline and dopamine .. would need to read up.. but I also have tested strangely low at times for the catcholamines as in right before I started freddd like doses.. very strange. but I also testd low in tyrosine which I do think is a precurer and Rich wil have to speak to this, but I think he mentioned tyrosine being low as an issue with not methylating properly?

Maybe and out on a limb why I have heard another MD say that adrenaline is actually low when you are not methylating. ??? So an uptick in adrenaline could be s sign you are methylating.. which would validate freddd but also still yasko..??

Hi, Soulfeast,

Do you think you could start your own thread about this? I have no idea what you and Rydra are talking about, and it's not clear to me what this has to do with folates and methylation.

The adrenalin relationship with methylation is interesting, and I'd love to hear more if you find references.

Thanks!

Madie
 

soulfeast

Senior Member
Messages
420
Location
Virginia, US
It has to do with whether folates and methylation _trigger_ hyperadrenergic states in some people, esp who have COMT++ status. Seems you don't. But that does not mean this does not relate to folates and methylation at all..

Hi, Soulfeast,

Do you think you could start your own thread about this? I have no idea what you and Rydra are talking about, and it's not clear to me what this has to do with folates and methylation.

The adrenalin relationship with methylation is interesting, and I'd love to hear more if you find references.

Thanks!

Madie
 

maddietod

Senior Member
Messages
2,859
It has to do with whether folates and methylation _trigger_ hyperadrenergic states in some people, esp who have COMT++ status. Seems you don't. But that does not mean this does not relate to folates and methylation at all..

Thanks for the translation!;)
 

soulfeast

Senior Member
Messages
420
Location
Virginia, US
:) I am constantly battling adrenaline I think because of the comt++ polymorphisms. I may be totally butchering the facts.. simplist way I understand it is that comt polymorphisms reduced or slow down the break down of methly groups.. so we are supposed to have a good supply on hand in the body. Additional methyl donors (like from MB12 and metafolin) make this methyl pool even larger and somehow this pool interfers with the processing or reuptake of adrenaline and dopamine. We are said to have 4 times the amount of your average peron in the body already. Yasko thus recommends using methyl groups only as needed and using HB12 instead of MB12 becasue the effect is truly overwhelming when living in a sea of adrenaline.. so how to dose metafolin and Mb12 if the latter is truly needed. I think MTHFr heterozygous extablished the need for the metafolin. I cant touch caffiene or any adrenergic medication. I just cant clear it well. Yasko would chose methyls "wisely" choosing metafolin over Mb12 for most (if not all comt++ folks). Then we have the dosing issue.. low vs high.

I'm not sure there is much more for Rosebud and I to discuss about it,but if there is, it would probably be best as a new thread. :)

Thanks for the translation!;)
 

maddietod

Senior Member
Messages
2,859
Soulfeast -

This is interesting timing. I tried the SMP (hb12) for 9 months with tiny results. I switched to the active protocol but kept the hb12 instead of mb12 and adb12. Some good stuff happened. About 2 weeks ago I added 250mcg mb12 daily, and I've seen big changes. And...in the last 2-3 days, my reaction to small amounts of caffeine got huge.

Throughout this, I've been taking varying amounts of metafolin, but the biggest single shift has come from the b12. At the moment I'm taking 400mcg of metafolin.

I'm +/- for COMT V158M and H62H.


For those following the potassium piece of my experiments, as soon as I dropped my metafolin down, I stopped needing potassium. Because my potassium has always been in the low-normal range, I bought a meter, and I'm testing fine.

Healing is apparently proceeding well: yesterday my brain was clear all day, my emotions were strong and stable, and my energy was high. I shopped for mountains of vegetables, cooked and juiced a lot of it, and raked leaves/pulled wisteria runners. I'm fine this morning.
 

rydra_wong

Guest
Messages
514
I am posting this interesting study I found here about folate. This has interest for me because I keep getting iron deficient. It basically says that your MCV may be ARTIFICIALLY LOW if you are low in ferritin (as I have been my whole life). So - I have never had an abnormal MCV, but that means nothing. I have never once in my whole life had a ferritin above 50. So...! Just thought others might want to be alert to this.


http://www.lef.org/abstracts/codex/iron_abstracts_02.htm
Unanticipated favorable effects of correcting iron deficiency in chronic hemodialysis patients.
Polak VE, Lorch JA, Means RT Jr.
BACKGROUND: Correction of anemia in hemodialysis patients is seldom completely attained, and the response of parameters other than hemoglobin concentration to anemia correction has not been evaluated in detail. METHODS: Laboratory parameters that suggest iron deficiency occurred in 1015% of 206 recombinant human erythropoietin (rhEPO)treated patients. Oral iron was given for 9 months and intravenous iron thereafter on a patientspecific basis when iron deficiency was evident. Eightyseven hemodialysis patients with data for 12 months were followed for another 12 months. A computerized information system enabled data management and analysis. RESULTS: With oral iron, serum ferritin decreased (P < 0.001), indicating further iron depletion. With intravenous iron, hemoglobin increased, evidence of iron deficiency decreased, and less rhEPO was needed. Striking macrocytosis appeared. Serum albumin and serum creatinine/kg body weight (an index of muscle mass) increased, while blood pressure decreased. Data were reanalyzed in four mean corpuscular volume (MCV) quartiles and two ferritin subsets at study onset. Iron deficient erythropoiesis (low MCV, mean corpuscular hemoglobin [MCH], and transferrin saturation) was striking in quartile 1; low ferritin was prevalent in all quartiles. With intravenous iron, hemoglobin increased only in quartile 1, the quartile with the greatest decrease (52%) in rhEPO dose. MCV increased in all quartiles (P < 0.001). Serum albumin increased in all MCV quartiles and both ferritin subsets, but significant creatinine/kg increase and blood pressure decrease occurred only in the lowferritin subset. CONCLUSIONS: Macrocytosis occurred with intravenous iron replacement. The universal MCV increase suggests unrecognized, inadequately treated, folic acid deficiency unmasked by an adequate iron supply. There was also improved well being. Effects were most clearly evident in patients with deficient iron stores. PMID 11288758

-----

P.S.I am not saying one needs a lot of mfolate. I think my low dose is fine for me, but when I get my iron up (IF I can) I guess I will know for sure. (When I take iron it goes to serum Fe, not so much to ferritin...I believe I do not have enough retinol binding protein or something...not sure just yet).
 

maddietod

Senior Member
Messages
2,859
Things are still very non-linear over here. I bought a potassium meter, because tests going back over 10 years show me consistently at the bottom of normal. This has proven useful, as I do slip below normal when I don't supplement, and no matter what I do, I can't get up to the blood level-equivalent of 4 (normal range is 3.5-5.2). So I don't have a lot of wiggle room if methylation does grab lots of potassium. Good to know.

I gave up on the folates + metafolin experiment. The idea was that since I feel (relatively) fabulous on an all-protein diet, I probably had paradoxical folate deficiency. And so what I needed to do was figure out how much metafolin to take throughout the day and with food, to feel fabulous while eating X amount of vegetable folates. But no amount of metafolin produced that result.

So currently I'm thinking about this in terms of limiting factors. This might not be the problem, but it's what I'm playing with right now. Keeping my potassium up fixes a specific group of symptoms (tightness, a certain kind of emotional sensitivity)...so low potassium was plugging up the works somehow.

I'm still figuring out the best ways to work with potassium. If anybody knows how long the gap is between ingestion (tablets or food) and a change in salivary levels, I'd love to know that. I drank a quart of coconut water yesterday (2000mg potassium) and 4 hours later my saliva reading was unchanged.

Starting yesterday, I doubled my dose of mb12. I'm now taking 250mcg am and mid-afternoon, and I'm splitting my dose of hb12, taking one drop with each mb12. In case I need the metafolin simultaneously, I take a B Complex (400mcg) in the morning, and one Solgar (800mcg) in the afternoon.

I've gotten some obvious gains. Lifelong psoriasis on my ankles is gone, first time ever. It persists on my elbows. Other small rashes on my hands, torso, and legs have also disappeared. I have more physical stamina, in short-ish bursts, without PEM. Now that the weather has warmed, I get out every 2 days or so and rake or pull up vines for an hour or more. Socially, it's much easier for me to be around friends. Not that I do it often - I'll always be an introvert - but it doesn't feel like a crushing burden.
 

Dreambirdie

work in progress
Messages
5,569
Location
N. California
I as well had a noticeable benefit even from a small amount of methyl b12. Half or a quarter of a an Enzymatic Therapy tablet.

I also use a very low dose of MB12, (about 25-500 mcg), when I wake up too early in the morning. It helps calm my brain down so I can get back to sleep. I take other things with it (L-tryptophan, magnesium and Chinese herbs for sleep), but I noticed that adding the MB12 made those other things more effective.

I have to be careful to NOT take the HB12 or the methylmate on the days I take the MB12, and to not do any of these supp's more than 4 days/week total, or else I begin to detoxify too heavily. It is definitely a delicate balance.
 

Dreambirdie

work in progress
Messages
5,569
Location
N. California
Starting yesterday, I doubled my dose of mb12. I'm now taking 250mcg am and mid-afternoon, and I'm splitting my dose of hb12, taking one drop with each mb12. In case I need the metafolin simultaneously, I take a B Complex (400mcg) in the morning, and one Solgar (800mcg) in the afternoon.

I've gotten some obvious gains. Lifelong psoriasis on my ankles is gone, first time ever. It persists on my elbows. Other small rashes on my hands, torso, and legs have also disappeared. I have more physical stamina, in short-ish bursts, without PEM. Now that the weather has warmed, I get out every 2 days or so and rake or pull up vines for an hour or more. Socially, it's much easier for me to be around friends. Not that I do it often - I'll always be an introvert - but it doesn't feel like a crushing burden.

I'm glad to hear you are having some positive changes. Being able to do some raking and pulling vines is quite impressive!

As far as the K levels in your saliva.... just wondering how accurate of a K reading one can get from saliva? and how that compares with K in blood? It's also tricky to know how well your blood is transferring the K from the saliva to the blood? And also, what is "normal" K for someone who is in the midst of a methylation protocol?

I think I would rather trust my instincts than to have to figure all this out. As long as I was feeling relief from certain pressing symptoms, I would feel like I was on the right track.
 

L'engle

moogle
Messages
3,197
Location
Canada
Hi Madie, DB, Rydra, Topaz, Freddd and others (sorry I forget who is part of this conversation!)

Like Madie, I need potassium constantly. If I don't take it several times in the day I get a stabbing sensation in the back of my calves and increased fatigue. I get enough improvement from the B12 and folate that it is worth it. Like Madie, I have been trying to duplicate the effects of avoiding vegetable food folates. I had one day where I felt markedly better, but if I recall it was after I had taken 16 X 800mcg metafolin in a day and then avoided food folate the next day, and felt improvement on the day after that. I haven't gone two consecutive without vegetables since then, as it feels unhealthy in other ways.

For the past week my plan has been to avoid vegetable folate every other day, and take 16 X 800mcg metafolin on the opposite day. I messed up my own results though by trying out a new supplement on the fifth day that interfered with my sleep and left me feeling ill on the 6th and 7th days, so I don't have a clear reading yet and will continue the opposing day schedule for at least another week. I did have a relatively good week in regards to brain fog, which is the main symptom I'm attacking right now. However it wasn't startling out of line with what I have experienced.

I will let you all know how the second week of this ridiculous one day off one day on diet/supplement plan works. Not sure I'd recommend it to anyone as of yet.