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Above lab range Folate and high B12?

Hi guys,

I already red quite a few things about the Methylation issues/cycle etc. but theres so much information that im getting slightly confused...

During different lab tests the one thing that always popped up for me is that my folate was above lab range high (upper limit i think 25 and i landed at 45) and my B12 is always on the top of the range.

Im suffering from CFS, fatigue, feeling intoxicated, energy crashes, sleeping issues. I made the 23andme gene testing to check for MTHFR and Detox abilities (my results are here: http://forums.phoenixrising.me/inde...livewello-profile-where-should-i-start.45269/).

As far from what ive read it could be that my folate pools in the blood and is not able to actively reach the cells? Ive tried MethylB12 and L-5-MTHF for 2 weeks and i seemed to get a bad reaction to it after a while (started slowly with 200mcg of L5-MtHF and 500mcg of MethylB12), got back my anxiety issues and felt quite wired, no real symptom relieve or amelioration.... Tried the Thorne methylated B Complex and it made me feel a lot worse, i dont seem to tolerate any B-Vitamine Complex (anxiety, strong brainfog, worsened fatigue, really spacy derealised feeling)
What im wondering is if I could have an issue there and how to solve it properly? I dont seem to have the MTHFR Mutation (see my results) could there be another issue causing this folate buildup?
My b12 is high no doctor would say that i have a defiency as well as the folate but i have all the symptoms...

thanks a lot in advance for any help!

Greetings from Germany


Senior Member
Which lab test did you do for folate? The reason I ask is if the lab doesn't separate folic acid from folate, your high range could be because you have high folic acid levels. This would likely be from eating foods enriched with folic acid. I see you're in Germany and I don't know if they enrich their white flours and other cereals with folic acid like here in N America. Folic acid can block natural folate from reaching folate receptors.

Here's a breakdown of the different folates that can be tested for and what results would mean (from Rich Vank):

5-CH3-THF: This is a measure of the concentration of 5L-methyl
tetrahydrofolate in the blood plasma. The reference range is 8.4 to 72.6 nanomoles per liter.

This form of folate is present in natural foods, and is normally the most abundant form of folate in the blood plasma. It is the form that serves as a reactant for the enzyme methionine synthase, and is thus the important form for the methylation cycle. It is also the only form of folate that normally can enter the brain. Its only known reactions are the methionine synthase reaction and reaction with the oxidant peroxynitrite.

When there is a partial block in methionine synthase, the other forms of folate continue to be converted to 5L-CH3-THF by the so-called “methyl trap” mechanism. Some of the 5L-CH3-THF is broken down by reaction with peroxynitrite, which results from the condition of oxidative stress that is usually concomitant with glutathione depletion.

Many PWCs have a low value of 5L-CH3-THF, consistent with a partial block in the methylation cycle. Most methylation treatment protocols include supplementation with 5L-CH3-THF, which is sold over-the-counter as Metafolin, FolaPro, or MethylMate B (trademarks), as well as the newer Quatrefolic (trademark) and in the prescription “medical foods” supplied by PamLab, including Deplin, CerefolinNAC and Metanx. There are some others on the market that include both racemic forms (5L and 5R) of this folate.

When methylation treatment is used, the level of 5-CH3-THF rises in nearly every PWC. If the concentration of 5-CH3-THF is within the reference range, but either SAM or the ratio of SAM to SAH is below the reference values, it suggests that there is a partial methylation cycle block and that it is caused by inavailability of sufficient bioactive B12, rather than inavailability of sufficient folate. A urine organic acids panel will show elevated methylmalonate if there is a functional deficiency of B12. I have seen this combination frequently, and I think it demonstrates that the functional deficiency of B12 is the immediate root cause of most cases of partial methylation cycle block. Usually glutathione is low in these cases, which is consistent with such a functional deficiency. As the activity of the methylation cycle becomes more normal, the demand for 5-CH3-THF will likely increase, so including it in the treatment protocol, even if not initially low, will likely be beneficial.

10-Formyl-THF: This is a measure of the concentration of 10-formyl
tetrahydrofolate in the blood plasma. The reference range is 1.5 to 8.2 nanomoles per liter.

This form of folate is involved in reactions to form purines, which form part of RNA and DNA as well as ATP. It is usually on the low side in PWCs, likely as a result of the methyl trap mechanism mentioned above. This deficiency is likely the reason for some elevation of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) often seen in PWCs. This deficit may also impact replacement of cells lining the gut, as well as white blood cells.

Rarely, 10-formyl-THF is found to be much higher than the normal reference range. If this is found, the patient should be examined for cancer, since cancer cells upregulate this form of folate in order to make purines more rapidly to support their rapid cell division.

5-Formyl-THF: This is a measure of the concentration of 5-formyl
tetrahydrofolate (also called folinic acid) in the blood plasma. The reference range is 1.2 to 11.7 nanomoles per liter.

This form is not used directly as a substrate in one-carbon transfer reactions, but it can be converted into other forms of folate, and may serve as a buffer form of folate. Most but not all PWCs have a value on the low side. It is one of the
supplements in some methylation protocols. It can be converted to 5L-CH3-THF in the body by a series of three reactions, one of which requires NADPH, and it may also help to supply other forms of folate to the cells until the methionine synthase reaction comes up to more normal activity.

THF: This is a measure of the concentration of tetrahydrofolate in
the blood plasma. The reference range is 0.6 to 6.8 nanomoles per liter.

This is the fundamental chemically reduced form of folate from which several other reduced folate forms are synthesized, and thus serves as the “hub” of the folate metabolism. THF is also a product of the methionine synthase reaction, and participates in the reaction that converts formiminoglutamate (figlu) into glutamate in the metabolism of histidine. If figlu is found to be elevated in a urine organic acids panel, it usually indicates that THF is low. In PWCs it is lower than the mean normal value of 3.7 nanomoles per liter in most but not all PWCs.

Folic acid: This is a measure of the concentration of folic acid in
the blood plasma. The reference range is 8.9 to 24.6 nanomoles per liter.

Folic acid is a synthetic form of folate, not found in nature. It is added to food grains in the U.S. and some other countries in order to lower the incidence of neural tube birth defects, including spina bifida. It is the oxidized form of folate, and therefore has a long shelf life and is the most common commercial folate supplement. It is normally converted into THF by two sequential reactions catalyzed by dihydrofolate reductase (DHFR), using NADPH as the reductant. However, some people are not able to carry out this reaction well for genetic reasons, and PWCs may be depleted in NADPH, so folic acid is not the best supplemental form of folate for these people.

Low values suggest folic acid deficiency in the current diet. High values, especially in the presence of low values for THF, may be associated with inability to convert folic acid into reduced folate readily, such as because of a genetic polymorphism in the DHFR enzyme. They may also be due to high supplementation of folic acid.

Folinic acid (WB): This is a measure of the concentration of folinic acid in the whole blood. The reference range is 9.0 to 35.5 nanomoles per liter.

See comments on 5-formyl-THF above. Whole blood folinic acid usually tracks with the plasma 5-formyl-THF concentration. They are the same substance.

Folic acid (RBC): This is a measure of the concentration of folic acid in the red blood cells. The reference range is 400 to 1500 nanomoles per liter.

The red blood cells import folic acid when they are initially being formed, but during most of their lifetime, they do not normally import, export, or use it. They simply serve as reservoirs for it, giving it up when they are broken down.

Many PWCs have low values of this parameter. This can be caused by a low folic acid status in the diet over the previous few months, since the population of RBCs at any time has ages ranging from zero to about four months. However, in CFS it can also be caused by oxidative damage to the cell membranes, which allows folic acid to leak out of the cells. Dr. Audhya reports that treatment with omega-3 fatty acids has been found to raise this value over time in one cohort.

Which lab test did you do for B12? Levels in the blood don't tell whether the B12 is getting into your cells and being used. High blood levels can mean the B12 is floating around in your blood unable to be transported into your cells for various reasons. Methylmalonic acid (MMA) testing is probably the most accurate test for B12 deficiency.

Hello Helen,

thank you for the quick reply!
I have done tests from several doctors and several labs. I didnt research on Folate or B12 at that time they did big blood screenings with their routine paramters.
I've checked all the paperwork and made a copy, there is no specification on which one, i guess its the total folate? B12 not specified either... even though its different labs.

I dont eat any processed food anymore, no cereals, gluten free and histamine low diet. from what i eat everyday nothing of it says folic acid on the ingredient list.

What do you think? I clearly have an issue and wonder if it could be methylation/detox.. What would you say i should do? cant i start trying something and by the reaction tell if its the good way?

here goes all the lab values, ive attached the genetic results as well maybe that helps interpretation
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Methylation has become an alternative health "fad", so be careful with your approach. You'll notice that many of the people here promoting the megadosing of B12/B9 are still searching for answers.

Every single B vitamin modulates blood sugar at some level. It's a temporary effect and it typically relates to changes in epinephrine; folate in particular. Put some faith in your original lab results and move away from unnecessary supplementation.

Judging by your symptoms, you may have some form of reactive hypoglycemia. Niacin can potentially give you some short term relief if you can handle it. The flush causes a histamine response that temporarily suppresses adrenaline, and increases blood glucose. Be sure to take it at night before bed.

Blood sugar management is a lifestyle. You can't cure it with Deplin and bottle of methylB12 lozenges ;)

i have reactive hypoglycemia i had a 5 hour blood sugar test for that. BUT in my opinion this is a symptome of something else... when i feel good my blood sugar stays stable, when i dont i seem not to get it stable even with eating very often... ive payed a lot of attention to how eating effects my symptoms.. my health picture is just too big just to be caused by fluctuating blood sugar levels, thats what my doctors confirmed as well...
Its not normal having to eat every 2 or 3 hours to get aproximatly normal sugar lvls

Sometimes i dont wake up with low sugar lvl at night, sometimes i do (even though i always eat a huge meal before bed, if i dont eat before bed obviously i get issues)


Senior Member
Hi @splaszzz ,

The elevated folate could be caused by the overgrowth of folate producing bacteria in the intestines. The biggest producers of folates are lactobacillus and bifidobacteria genera. If overgrown, they can be pathogenic.

I suspect there could be other microbes that are causing symptoms.

The TCN1 snp means that B12 transport is difficult. This article recommends high dose B12 as treatment.

Mutations in the gene encoding TC (TCN1) result in severe tissue cobalamin insufficiency, megaloblastic anaemia, failure to thrive and often neurological complications, despite normal plasma cobalamin concentrations (Refs 71, 72). Additionally, TC acts as a final screening mechanism because, like IF, TC is very specific for cobalamin forms that have the lower DMB intact (Refs 73, 74). Treatment of TC deficiency requires very high serum cobalamin levels, ranging from 1000 to 10 000 pg/ml, achieved by oral or intramuscular delivery of 0.5–1.0 mg of CNCbl or HOCbl once or twice weekly (Refs 60, 75).
You've tried many combinations of B vitamins. Have you tried B12 alone?
HI @Crux

interesting, ive had a bacteria analysis done but thats several years ago when i was still doing "ok". i only remember having E Colis above high. My current doctors all say this bacteria analysis is not worth doing as research doesnt know yet which bacterias really cause issues/are important...

thank you a lot for the TCN1 snp interpretation! I tried with the snp interpretation guide and couldnt find any obvious "issues".

ive tried Methylcobalamin and methylfolate for 2 weeks which made me a little wired (started low) and after 2 weeks anxiety creeped back. now i read that i shouldnt use methylcobalamin according to my SNPs (which might explain my negative reaciton to it).

Which type of B12 would you use now? from reasearching my snps i found hydroxy to be the "good" choice? What would you say, should i start on that and try high doses (start low first) and see if i get an improvement?



Senior Member
Hi @splaszzz ,

It's true that microbiome analysis and testing are in the early stages. There's a lot of debate going on.

Not only is it difficult to get accurate testing, but a confusing factor in the analysis is the relationship between the microbes. ( competition, inhibition, etc.)

It's really confusing to me.

It's still worth a look, though. For instance, E. coli can be both beneficial and pathogenic. It produces vitamin K2, and B12. ( although the B12 supposedly isn't absorbed because it's produced lower in the intestines. I wonder.)

E. coli produces lactate, which can be good if not too much. Too much lactate can cause neurological damage.

The type of B12 people are using here has become very personalized.

Some are taking injections. This way avoids some of the additives and sweeteners that cause side effects.

Some are using transdermals with good results.

I'm still using sublinguals. In the past, the sweeteners caused a lot of gut problems. ( bacterial overgrowth)

After treatment, I can tolerate the sweeteners. ( I've reduced the dosage to 3 mgs. or less daily.)

With the choice of methylcobalamin or hydroxocobalamin, it looks to be personal again. ( I take both.)
Some folks find the methylcobalamin to be overstimulating.

Some of the symptoms you've listed may or may not be B12 related. ME/ CFS is...complicated. The recommendation is to start low, wait for changes, then increase as needed.


Hoarder of biscuits
Interpretive Handbook
Vitamin B12 and Folate, Serum

Nonfasting specimens yield falsely elevated results.
Patients taking folate may have misleading results.

Patients taking vitamin B12 supplementation may have misleading results.
Many other conditions are known to cause an increase in the serum vitamin B12 concentration including:

Ingestion of vitamin C
Ingestion of estrogens
Ingestion of vitamin A
Hepatocellular injury
Myeloproliferative disorder

ive started today with 1mg of hydroxy b12 sublingual from perque, so far no real real effect (kept it for 2 hours under my lip), im gonna take another 1mg later on the day and if i dont get any adverse effects start with 2mg tomorrow.

blood draw was twice made fasting and thats where folate was above range, the others were non fasting and above range as well....
so far ive tried Adb12, Hydroxy and Methylb12, MethylB12 = nervousness/anxiety. Hydroxy i get effects subtile i would say, adb12 no effect or worsening of the fatigue (its with folic acid though)...

But since ive tried out B12 hydroxy and Adeno for a couple of days my sleep has improved, might be a coincidence but its the first time for months that ive slept continuous 8,5 hours without waking up and needing to take more melatonin.. my blood sugar didnt break during the night either and my thirst at night was not there at all yesterday...

could that be the b12?