Folate: which one + what dose + what ratio with B12 + which B12 ?

Dr Rich,

* L-5-methyltetrahydrofolate (L-5-MTHF)
* 5-formyltetrahydrofolate (5-formyl THF)

Which of the above forms of folate is best, or is better to take both?

What is the maximum optimal dose to build up to (for each form if we take both)?

Is there a maximum upper safe limit we should not exceed?

What is the ratio we should aim for of folate:B12 or does it not matter, is a standard dose of 5000mcg B12 per day ok regardless of folate intake?

Does the ratio vary depending on whether its methylB12 or hydroxy B12?

Is it better to take a mix of methylB12 and hydroxy B12 or just one of them - which one is best?


Sorry for all the questions, especially if some are repetitive to other posts - thanks heaps in advance for clarifying?

sleepy

Unless you know for sure you don't have any MTHFR polymorphisms, it is a better bet to take methylfolate. Methylfolate will get converted to formylfolate anyway in the process of methylation. A common starting dosage for methylfolate is between 400 and 800mcg/day together with around 1mg/day of oral methylcobalamin. I am not much of a fan of hydroxocobalamin because it needs glutathione to do its job.

Hi, sleepy.

I think that Madie and nano have given you some good information. I don't think we can give a one-size-fits-all recommendation. That's what I hoped to do originally, but, as Winston Churchill used to write, I was "overtaken by the course of events." We humans seem to be a collection of odd balls--all different from each other in various respects.

You could try the Simplified Methylation Protocol:

http://forums.phoenixrising.me/show...ed-as-of-Today&p=168458&viewfull=1#post168458

and see how it goes. Or you could do some testing and try to tailor things to your particular case a little better.

I think we are mostly in agreement here that chemically reduced folate (at least including L5-methyl THF), at at least RDA-level dosages (400 to 800 micrograms per day), combined with high-dose B12 (hydroxo- or methyl-B12) (of the order of a milligram or two per day, either sublingually or by injection) is a necessary core of the treatment. Choosing between the two forms of B12 seems to depend on the individual, and beyond these supplements, there is a variety of opinions.

I posted what I see as the current status on another thread:

http://forums.phoenixrising.me/show...ME-CFS-today&highlight=understanding treating

I hope this is helpful.

Best regards,

Rich

foliat

Hi rich,
If my foliate level is high, should I still be taking foliat? I was using hydro b12 with folirinse(10%) potassium dilate solution a few times a day and crashed really badly. So I stopped and just do the b12. I am also taking valtrex 3gm a day and csm for detox. Just find't know if you could od on foliat.
Thanks, equestrian111

Hi, equestrian.

Folirinse contains folic acid. That's not the best form of folate to be taking. Some people cannot convert it very well to the active forms of folate. It also requires NADPH to do the conversion, and this can be low in ME/CFS and is also needed for other important reactions. There is some evidence that if folic acid is not converted and therefore builds up in the blood, it can inhibit the natural killer cells and may increase the risk of cancer. This is not agreed upon yet. Folic acid is an artificial, oxidized form of folate. It has a long shelf life and is relatively inexpensive, so it has been the main commercial form of folate, but the reduced forms have been produced in stable forms now and are available, so they are preferable.

Doing the methylation protocol at the same time as Valtrex and cholestyramine may be pretty challenging. It might be better to space these out.

Best regards,

Rich

. Thanks Rich,

Good to know. It's tough to be your own Dr. When you no very little . But at this point I know more about Mold and cfs than my GP. And that's not saying much. I will take your advise and skip the methy for now.
Equestrian111

Thanks Dr Rich (and others)

still a little confused (brain fog!)

the protocols say folinic acid (5-formyl THF) and Dr Rich you suggest "at least including some L5-methyl THF".

I have been on the protocol for a few months and taking 800mcg L5-methyl THF only and wondered if I should include 5-formyl THF as well?
Is it optimal to take both forms or doesn't it make much difference?
I had a standard blood test from my GP which said my MTHFR gene was ok (I assume this test would be accurate?).

Should the combination of both forms = 800mcg or can this amount be exceeded?

thanks

sleepy

Sleepy

Rich

You say that folic acid can build up in the body if it is not converted, but it is water soluble so how can that be?

Brenda

Hi, Brenda.

Yes, it is water soluble. It builds up in the blood stream if it is not converted. The kidneys are able to reabsorb it, so it doesn't go out in the urine at a very high rate.

Best regards,

Rich

Hi, sleepy.

I think that it is beneficial to most PWMEs to take folinic acid as well as L5-methyl THF. The reason is that folinic acid can in most cases be readily converted to other forms of folate, such as those needed to make RNA and DNA for the production of new cells. L5-methyl THF can't do that until it gets through the methionine synthase reaction, which is partially blocked in ME/CFS, and it takes time to get that reaction going. Freddd and some others are not able to use folinic acid, though, apparently for genetic reasons, and in that case, it should be avoided.

Optimum dosages seem to vary from one person to another. In the simplified protocol, I've suggested about 200 micrograms of each. Some people need more.

Best regards,

Rich

I have helped a lot of people find balance and as data accumulates it looks like this, which isn't what I would have expected by the way. I would habe thought to see more proportionality relationships.

methylb12 dose 15mcg absorbed estimated to 180mg injected daily
adenosylb12 dose - 15mcg absorbed to 10mg absorbed

Methylfolate - person without b12 deficiency, no B12 startup, no methylation startup, no ATP startup - 800mcg
Methylfolate - person with b12 deficiency, b12 startup, methylation startup, ATP startup - 1600-4000mcg
Methylfolate - person with b12 deficiency, methylation startup, ATP startup, paradoxical folate deficiency with folic acid, 6000-8000mcg
Methylfolate - person with b12 deficiency, b12 startup, ATP startup, paradoxical folate deficiency with folic acid and folinic acid-veggie-folate, 12mg +

Potassium - with b12 deficiency, B12 startup, methylation startup, ATP startup - 1600mg- 3000mg
Potassium - no deficiency, no cfs, no fms, no methylation startup, no ATP startup, no B12 startup, - 99mg

Methylfolate appears 100% sufficient when taken oin suitable amounts. Howefver, if a person has no problem with folinic acid there is no reason not to take it. If it causes "detox" that is usually paradoxical folate deficiency if you have made sure it isn't potassium deficiency.

As far as I can see there is no reason not to take folicnic acid but if it does block methlyfolate so will veggie folate and will cause paradoxical folate deficiency and prevent healing and cause worsening of symptoms. However, there is also no specific reason at all to not take it if your body can use it.

Methylfolate is necessary and sufficient.
Folinic acid is not necessary and not usually sufficient for the rate of healing that happens with even 15mcg of mb12 and 15mcg of ADb12.

You either need to take folinic acid AND Methylfolate OR Methylfolate.

Paradoxical Folate Deficiency was spotted first in a horse taking folic acid.

But why do some recommend not going over 800 mcg.? Like Yasko and in Rich's protocol? Rich or anybody?

My friend is on 15 mg. AdB12 and 5 mg. of MB12. Added 1 mg. Hydroxy B12 this week. 800 mcg. methylfolate in a.m., plus another 166 mcg. a.m. and 166 mcg. p.m. in Thorne multi. This has pretty much been at this level since February (except the new Hydroxy).

Is this enough folate? He recently started a brand new frightening symptom - numbness in mouth, jawline, limbs. Nothing has changed except I believe he is finally starting to rid toxins; is unusually tired for him. I did increase his potassium and magnesium. His naturopath said some think numbness can be a sign of low folate, but when I asked her if I should increase she didn't respond although I asked a lot of other questions too.

But wondering about the folate re: the numbness. Also hoping more folate may help his still slurry speech.

?any insights appreciated.

P.S. Sleepy, I didn't mean to take over your thread but I did a search and your questions were similar to mine so I didn't want to start a new one; hope you don't mind.

Hi Pea,

I think that the fear of folate comes from the massive "detox" that many people had with folic and folinic acid. "Detox" is a misnomer for paradoxical folate deficiency and for even mild potassium deficiency. When those are corrected almost all the "brand new frightening symptom" go away within hours to days. Toxins really have NOTHING to do with it maybe 99% of the time. It is this fallacious theory that has caused people years of unending misery when they can be done with it in hours..

There is a "donut hole" paradoxical folate deficiency in which 200mcg of Metafolin causes so much healing to start that one needs 3200mcg of folate to sustain and they get almost immediate folate insufficiency symptoms. People are not used to having real actually effective vitamins after decades of almost totally ineffective pseudo vitamins like hydroxycbl, cyanocbl and folic acid. Even worse some of us can't utilize vegetable folate and that can up the metafolin needs to 12-30mg or there abouts.

The slurry speech is very concerning. That can be CNS involvment. Does he have anxiety as a characteristic? If so a great deal of caution is needed and a slow titration. This probably can be corrected with the right combination and amounts of these various nutrients. The active b12 protocol can maybe deal with it, but hydroxycbl hasn't a snowflake's chance in hell.

Thanks, Freddd. The slurry speech isn't new - this is the main symptom that won't improve, even though many many other things have improved. Remember I asked awhile back why after a few times he had a beer, his speech sounded totally normal for a few words. One person thought maybe it was the folate. His naturopath thinks he needs dopamine, but now with the numbness I'm wondering if he needs more folate. Is numbness a folate insufficiency symptom?

He had anxiety, but that went away, until recently. He always was prone to anxiety though. It did get worse with the onset of symptoms, but a lot of that was ammonia which went away with enough Vitamin C. Actually I was using more of that Perque Potent Guard C which has ascorbate, calcium, magnesium, potassium, and zinc.

Maybe I should try a bit more of folate, I just wondered what the reasoning was for keeping it so low. I will also see how he does on the increased potassium & magnesium; hopefully that will help. Trying to get him to eat more fruits & veggies for the folate, potassium, & magnesium, and drink water, but it can be a chicken/egg roundabout, when he doesn't feel well then has swallowing problems, goes back to the comfort foods & so on.

that's what I'm trying to find - the right combination - because the voice is able to work, there's just something missing.

HI Pea, Is he stable on the 5mg of mb12? I would reverse the amounts of mb12 and adb12; 15mg of mb12 and 5mg of adb12. The I would add carnitine. It might me eaiest to get the Jarrow Liquid l-carnitine for a titration from a very low level so we can be precise with very small amounts if needed. I would have him start at 1mg to see the reaction. Then we need to get the other critical cofgactors going and see what kicks things off. It could be the carnitine which is why to start there. It may also be very extreme. But it needs to start somewhere.

Hi, pea.

I can't speak for Dr. Yasko, but the reason I don't recommend going much higher on methylfolate when it is combined with several milligrams of methyl B12 is that this combination takes control of the rate of the methionine synthase enzyme away from the cells and drives it too fast. The result is that too much of the homocysteine is converted to methionine, and there is not enough left to flow into the transsulfuration pathway to support synthesis of glutathione and other sulfur-containing substances that the cells need.

The result is that the methylation cycle gets going well, but glutathione does not come up, as it needs to do for full recovery. There are excess methyl groups produced because of overdriving the methylation cycle. These are shunted off to the folate metabolism by sarcosine, which is produced by the glycine N-methyltransferase reaction, and then they come back to the methylation cycle via methylfolate. It's sort of like a futile cycle, like a squirrel in a rotating cage.

This is not just based on biochemical theory, though it is supported by that. It is based on lab tests that people who have been on this regimen have sent me.

For most PWMEs, this does not work very well in the long run. In Freddd's own case, because of the genetic variations that he apparently has in the CblC complementation group and in MTHFS (not to be confused with MTHFR), it is necessary for him to use a high dosage of methyl B12 to overcome the CblC problem, and it is necessary for him to use a high dosage of methylfolate to feed his folate metabolism, since he cannot use folinic acid or folic acid. (I'm not sure why he cannot use folic acid. Perhaps he has a polymorphism in the DHFR enzyme, also). Freddd cannot tolerate raising glutathione, because it binds cobalamin to form glutathionylcobalamin, and his version of the CblC complementation group is not able to retrieve cobalamin from glutathionylcobalamin. As far as I can tell, this is a rare genetic variation. Most PWMEs are depleted in glutathione, and this is responsible for a large number of the symptoms.

There may be other PWMEs who have one or more of these genetic issues as well, since Freddd reports that there are some others who respond to these supplements in the same way he does, but most do not seem to have them, based on our clinical study and anecdotal reports from quite a few PWMEs.

Best regards,

Rich

Anyone use the folate suppllement called QuatreActiv folate? It says 4th generation methyl folate supp. Doctors best and nutricology sell it. Jarrow formulas I think just started also. Can not take solgar due to mannitol. Have a hard time with some sublingual b's due to mannitol sorbitol too, thankfully jarrow b12 only uses xylitol. Don't know why xylitol doesn't cause the massive stomach-gas-bloating like mannitol does for me. Beware of sugar free candies if you have this problem like me. You won't be able to leave the house for sure lol.

Hi Rich,

I don't recommend going much higher on methylfolate when it is combined with several milligrams of methyl B12 is that this combination takes control of the rate of the methionine synthase enzyme away from the cells and drives it too fast.

You need to consider that the experience piling up isn't at all reflective of this. Healing turns on with about 50mcg of mb12 and appears to typically require 1600-3200mcg of Metafolin in the absence of paradoxical folate deficiency.

With FMS, CFS, ME symptoms and healing response started (methylation startup), and no apparant paradoxical folate deficiency:

Potassium 1600-3000mg
at 50mcg of mb12/adb12 absorbed - 1600-3200mcg of metafolin
at 1mg of mb12/adb12 absorbed - 1600-3200mcg
at 5mg of mb12/adb12 absorbed - 1600-3200mcg of metafolin
at 40mg of mb12/adb12 absorbed 1600-3200 mcg of metafolin

Without FMS, CFS,ME symptoms and no healing response started, no paradoxical folate deficiency appararant, methylation was never broken:

Potassium 99mg
at 50mcg of mb12/adb12 absorbed - 800 mcg of metafolin
at 1mg of mb12/adb12 absorbed - 800 mcg
at 5mg of mb12/adb12 absorbed - 800 mcg of metafolin
at 20mg of mb12/adb12 absorbed 800 mcg of metafolin

With FMS, CFS, ME symptoms and healing response started (methylation startup), and apparant paradoxical folate deficiency - folic acid:

Potassium 1600-3000mg
at 50mcg of mb12/adb12 absorbed - 6000-8000 mcg of metafolin
at 1mg of mb12/adb12 absorbed - 6000-8000 mcg
at 5mg of mb12/adb12 absorbed - 6000-8000 mcg of metafolin
at 40mg of mb12/adb12 absorbed 6000-8000 mcg of metafolin

With FMS, CFS, ME symptoms and healing response started (methylation startup), and apparant paradoxical folate deficiency - folic acid and folinic acid:

Potassium 1600-3000mg
at 50mcg of mb12/adb12 absorbed - 12,000+ mcg of metafolin
at 1mg of mb12/adb12 absorbed - 12,000+ mcg
at 5mg of mb12/adb12 absorbed - 12,000+ mcg of metafolin
at 10mg of mb12/adb12 absorbed 12,000+ mcg of metafolin

You appear to be obsessed with mg of mb12. However, except for neurological healing 50mcg appears to work just as well for most people.

If I have observed this even approximately accurately it should be clear that quantity of mb12/adb12 beyond 50mcg makes no difference to the quantity of Metafolin or potassium in any kind of direct relationship. They don't have a feedback cycle where an increase in one requires an increase for the other. There are perhaps several quantum steps. There is the layer of epithelial healing set of by mb12, there is a layer of muscle healing set off by adb12-carnitine in addition to mb12, and there is a layer of neurological healing set off by both. The epithelial layer adds a large requirement for Metafolin. The muscle layer adds a need for Metafolin. The neurological layer which often requires the difference between 1mg of mb12 and 40mg of mb12 to have heal, doesn't increase the Metafolin need.

As far as I can tell, this is a rare genetic variation. Most PWMEs are depleted in glutathione, and this is responsible for a large number of the symptoms.

By selecting the right group, and that right group is those who have had a lot of healing from adb12/mb12/metafolin which were also those who have a big response to these things, say 75% of the people here more or less, one can see the effect of glutathione on approximately 100% of persons, the same or similar enough response to glutathione that it is indistinguishable without lab tests. That doesn't sound rare at all. First they heal and then the healing can be reversed by glutathione with full predictablity. You can bet on it near 100%. This group of people have lots of symptoms because the the active b12s deficiency causes hundreds of symptoms and also can relieve hundreds of symptoms without any of this struggling to fit a camel through the eye of a needle. Rare should make it difficult to find. Maybe ME-FMS-CFS selects for such people and puts all us bad eggs in one basket. The results I get with glutathione can be matched by almost everybody here. Even the people saying it relieves some of their symptoms are having relief by getting rid of the discomfort caused by Metafolin and Mb12 becasue it of the exact same effects of glutathione. The people who find comfort are so deep in deficiency they are ultra sensitive to mb12-metafolin and don't have the return of symptoms becasue theirs have never left and so the relief is the relief of returning to deep deficiency and getting rid of that pesky startup.

There may be other PWMEs who have one or more of these genetic issues as well, since Freddd reports that there are some others who respond to these supplements in the same way he does, but most do not seem to have them, based on our clinical study and anecdotal reports from quite a few PWMEs.

Rich, I can give you precise written directions on how to precisely reproduce the results I have gotten personally and in the N=10 trial, which had 100% results similar to mine. I've run into one person so far put into the hospital by glutathione "detox" response who is very dissimiler to me in all sorts of ways and a much more limited deficiency set and no paradoxical folate deficiency at all. The difference, in N=10 trial, was a difference in dose size and frequency, and how severe the response was. There was some variation in response. The several most severely neurologicall damaged people had the quickest furthering of neurological damage. Some of the people here are all frothed up about the theoretical possiblity of overmethylation (no known examples, but I am certainly looking) or mercury (highly uncertain, low probablity comparatively, and I am certainly looking for the clues), so severely that they won't even get methylation going in the first place and yet here you are ignoring that some percentage, perhaps a third or a quarter or half could have increased brain damage/cord damge in 6 weeks of gutathione or precursor usage.