Labs confirmation or move forward?

[zrbarnes]

Short version of my question:

If I've been taking methyl b12 and metafolin for a week and noticed positive results, should I stop taking them and go get lab work done to confirm I have an issue (and see if I have any related issues, such as potassium deficiency)? If so, how long do I need stop taking them before the lab work? What specific lab work would be good to have done?


Long version of my question: (if you are interested in my background)

I've been trying to treat what my doctor calls "ADHD Primarily Inattentive" type. More accurately, all my symptoms fall under what is generally known as SCT (sluggish cognitive tempo) on the internet, but not yet recognized as a real thing by my doctor. After going through several trials of different drugs, mostly stimulants, I've settled on using Selegiline, a selective, type-B MAOI. It's working fairly decent with it's low side effects profile and subtle action. The fact that it reduces oxidative stress of the brain was a big selling point for me. However, I still have issues with lack of motivation, trouble getting out of bed, etc.

The doctor has been doing his thing trying to figure out how to treat me as having ADHD-PI, but in the meantime I've been researching other possibilities on my own. My symptoms have a lot of overlap with b12 deficiency and CFS, so I've been researching them as well. I mentioned lab tests for vitamins/minerals/heavy metals before and was pretty much scoffed at since I am "in otherwise decent health", with a decent diet. He wanted to put me on antidepressants (SNRI's), but my serotonin system functions perfectly, so I never touched them. Why potentially create problems with something that isn't broken? I now have a new doctor who is open to different ideas, and isn't interested in pumping me full of amphetamines or potentially damaging mood enhancers.

Recently, I decided to check into methylation related supplements (sam-e, methylcobalamin, TMG, and methylfolate), specifically in relation to their effects on COMT inhibition. I picked up a bottle of Jarrow's Sublingual 1mg Methylcobalamin.

I will say this real quick: I have tried several medicines, supplements, herbs, etc. over the last year, trying to treat this. Very few have much effect on me (I'm apparently "immune" to the placebo effect). However, from the very first day I took the methyl b12, I felt... different. My body didn't ache as much. I felt more energetic, though I did feel a little bit "high on life," so to speak, with my head floating around in the clouds. After about 4 days of taking it twice a day, I started to not feel as much "floatey head" anymore. I also picked up some Solgar Folate 800mcg, NOW TMG, NOW potassium gluconate, and some SAM-e, and started taking them throughout the last couple days. I've already been taking Magnesium L-Threonate and Fish Oil, twice a day for months. I have plans to pick up some adenosyl b12 soon, after reading around on this forum. (EDIT: I just place an order for Jarrow's 5mg Methyl B12 Sublinguals and Source Naturals 10mg Dibencozide Sublinguals)

In about 6 months, I will lose my current medical insurance coverage. Because of that, I need to prioritize what medical work I plan to have done. It would be nice to have some kind of confirmation via lab test to determine if I actually do have issues with B vitamins/methylation. I've had a few positive life changes lately, which could (very unlikely) account for the sudden "good times" effect (though I doubt it, since the physical and mental change was substantial when I first started taking the methyl b12).

Since I have been taking the methyl b12 for about a week, does anyone have any recommendations how to proceed, such as: which tests to have done, if I should stop taking the vitamins for a certain period of time to get valid test result, etc...? I hate to get a bunch of lab work done and have the results come back negative just because I am taking the supplements. I don't know how long it would take to work them out of my system to get accurate numbers.

Any input would be lovely. Thanks!

 

[Freddd]

Short version of my question:

If I've been taking methyl b12 and metafolin for a week and noticed positive results, should I stop taking them and go get lab work done to confirm I have an issue (and see if I have any related issues, such as potassium deficiency)? If so, how long do I need stop taking them before the lab work? What specific lab work would be good to have done?


Long version of my question: (if you are interested in my background)

I've been trying to treat what my doctor calls "ADHD Primarily Inattentive" type. More accurately, all my symptoms fall under what is generally known as SCT (sluggish cognitive tempo) on the internet, but not yet recognized as a real thing by my doctor. After going through several trials of different drugs, mostly stimulants, I've settled on using Selegiline, a selective, type-B MAOI. It's working fairly decent with it's low side effects profile and subtle action. The fact that it reduces oxidative stress of the brain was a big selling point for me. However, I still have issues with lack of motivation, trouble getting out of bed, etc.

The doctor has been doing his thing trying to figure out how to treat me as having ADHD-PI, but in the meantime I've been researching other possibilities on my own. My symptoms have a lot of overlap with b12 deficiency and CFS, so I've been researching them as well. I mentioned lab tests for vitamins/minerals/heavy metals before and was pretty much scoffed at since I am "in otherwise decent health", with a decent diet. He wanted to put me on antidepressants (SNRI's), but my serotonin system functions perfectly, so I never touched them. Why potentially create problems with something that isn't broken? I now have a new doctor who is open to different ideas, and isn't interested in pumping me full of amphetamines or potentially damaging mood enhancers.

Recently, I decided to check into methylation related supplements (sam-e, methylcobalamin, TMG, and methylfolate), specifically in relation to their effects on COMT inhibition. I picked up a bottle of Jarrow's Sublingual 1mg Methylcobalamin.

I will say this real quick: I have tried several medicines, supplements, herbs, etc. over the last year, trying to treat this. Very few have much effect on me (I'm apparently "immune" to the placebo effect). However, from the very first day I took the methyl b12, I felt... different. My body didn't ache as much. I felt more energetic, though I did feel a little bit "high on life," so to speak, with my head floating around in the clouds. After about 4 days of taking it twice a day, I started to not feel as much "floatey head" anymore. I also picked up some Solgar Folate 800mcg, NOW TMG, NOW potassium gluconate, and some SAM-e, and started taking them throughout the last couple days. I've already been taking Magnesium L-Threonate and Fish Oil, twice a day for months. I have plans to pick up some adenosyl b12 soon, after reading around on this forum.

In about 6 months, I will lose my current medical insurance coverage. Because of that, I need to prioritize what medical work I plan to have done. It would be nice to have some kind of confirmation via lab test to determine if I actually do have issues with B vitamins/methylation. I've had a few positive life changes lately, which could (very unlikely) account for the sudden "good times" effect (though I doubt it, since the physical and mental change was substantial when I first started taking the methyl b12).

Since I have been taking the methyl b12 for about a week, does anyone have any recommendations how to proceed, such as: which tests to have done, if I should stop taking the vitamins for a certain period of time to get valid test result, etc...? I hate to get a bunch of lab work done and have the results come back negative just because I am taking the supplements. I don't know how long it would take to work them out of my system to get accurate numbers.

Any input would be lovely. Thanks!

Hi Zrbarnes,

If I've been taking methyl b12 and metafolin for a week and noticed positive results, should I stop taking them and go get lab work done to confirm I have an issue (and see if I have any related issues, such as potassium deficiency)? If so, how long do I need stop taking them before the lab work? What specific lab work would be good to have done?

You might have to stop for 5 years or so in order to get it down to where it was before starting the b12. It's already too late to know what it was. If you have low potassium that would be good to know and is a cheap test as part of a CBC. However, when it hits you if it does you like it did me you will be on the floor screaming, unable to walk and difficult to crawl and nobody there to carry me. It took me 45 minutes to get the 20-25 feet to the kitchen where I had the potassium. When it hits you can't possibly get tested quickly enough to be of help. You need potassium immediately then, not in a week. Low enough potassium for long enough can be fatal. This is legitimately the most truely dangerous thing a person is likely to run into doing the active b12 protocol. You MUST have potassium on hand for your own safety. I run into trouble by the time it gets down to 4.2 while lab standards sometomes don't alert until 3.5.

You are doing well, don't stop. The most telling thing you can do is walk into the docs office and have everybody notice how much better you look.

 

[zrbarnes]

Hi Zrbarnes,

You might have to stop for 5 years or so in order to get it down to where it was before starting the b12. It's already too late to know what it was. If you have low potassium that would be good to know and is a cheap test as part of a CBC. However, when it hits you if it does you like it did me you will be on the floor screaming, unable to walk and difficult to crawl and nobody there to carry me. It took me 45 minutes to get the 20-25 feet to the kitchen where I had the potassium. When it hits you can't possibly get tested quickly enough to be of help. You need potassium immediately then, not in a week. Low enough potassium for long enough can be fatal. This is legitimately the most truely dangerous thing a person is likely to run into doing the active b12 protocol. You MUST have potassium on hand for your own safety. I run into trouble by the time it gets down to 4.2 while lab standards sometomes don't alert until 3.5.

You are doing well, don't stop. The most telling thing you can do is walk into the docs office and have everybody notice how much better you look.

I just placed an order for Jarrow's 5mg Methyl B12 Sublinguals and Source Naturals 10mg Dibencozide Sublinguals, so as soon as they get here, I think I will start following the protocol. I've already got the Jarrows 1mg Methyl B12, Solgar Metafolin, and Potassium Gluconate on hand.

I haven't felt any crazy muscle issues so far, probably because I wasn't as deficient as some of the bad cases (or maybe because I haven't started really following the protocol yet).

So I'm thinking I should have at least a standard CBC done. From there, I don't know what to do, or if that's enough to catch any potential problems. The doc mentioned thyroid/hormone tests, as well.

Thanks for your help!



EDIT (from the other thread):

Hi zrbarnes,

The tests might tell you how bad the damge is but they do NOT tell you how much the active b12 and Metafolin can help you or not. Only a trial can tell you, the same answer whether you have tests or not. If you have to pay and you don't have hundreds of dollars to spend on tests that CAN'T give you the answers you want why have the tests? Who are you trying to "prove" anything to? The problem is that the tests can't prove a thing but are required in some cases for the insurance to pay for 1 cyanocbl injection per month which isn't what you would be doing in any case.

I guess it's more for social reasons then much else, especially considering that health problems run in my family. I was thinking that if I could point to test results as proof, then my parents might be willing to take a different approach to the way they treat their symptoms. You could say I'm the family guinea pig

But what you say is true. My only other concern is that I might miss some other issue I might have by not getting blood work done. For instance, I've worked with a lot of bare electronics over the course of my life, which up until recently had lead in the solder. So heavy metals, mineral deficiency, and thyroid/hormone issues might show up if I were to get some testing done. I'll probably just get a standard CBC done and call it a day.

 

[Rosebud Dairy]

ADD/ADHD are definitely treatable with this protocol. I have seen marvelous results, though they were not sustained because (MAYBE MAYBE) of some accidental folic acid consumption on my part turned my brain back to mush, and brought on a return of many many subtle neuropathy symptoms, which tend to die back down after a few days of careful diet. I swear the more Folic acid fortified foods I eat, the more my brain goes to mush. The less of them I eat, the sharper I am. Still figuring out if folinic acid does it to me also. L-methylfolate and related critical co-factors are helping not need to go back to the doc to check with her one more time about my ADD!!

Blood work can help some

 

[Freddd]

I just placed an order for Jarrow's 5mg Methyl B12 Sublinguals and Source Naturals 10mg Dibencozide Sublinguals, so as soon as they get here, I think I will start following the protocol. I've already got the Jarrows 1mg Methyl B12, Solgar Metafolin, and Potassium Gluconate on hand.

I haven't felt any crazy muscle issues so far, probably because I wasn't as deficient as some of the bad cases (or maybe because I haven't started really following the protocol yet).

So I'm thinking I should have at least a standard CBC done. From there, I don't know what to do, or if that's enough to catch any potential problems. The doc mentioned thyroid/hormone tests, as well.

Thanks for your help!



EDIT (from the other thread):



I guess it's more for social reasons then much else, especially considering that health problems run in my family. I was thinking that if I could point to test results as proof, then my parents might be willing to take a different approach to the way they treat their symptoms. You could say I'm the family guinea pig

But what you say is true. My only other concern is that I might miss some other issue I might have by not getting blood work done. For instance, I've worked with a lot of bare electronics over the course of my life, which up until recently had lead in the solder. So heavy metals, mineral deficiency, and thyroid/hormone issues might show up if I were to get some testing done. I'll probably just get a standard CBC done and call it a day.

Hi zrbarnes,

Absolutely get the thyroid. Hypothyroid is very common in this group. If you have Hashimotto's Thyroiditis in the active phase it can sometimes reverse with the active b12s protocol. Also, have hormones tested. CBC is good and make sure potassium is included, mutisegmented neutraphils. Make sure you get all the numbers, not just alerts or "in range" since a lot of problems can be obvious even from "in range" numbers.

However, one can get carried away with the testing and think that statistical averages and 2 SD can tell them things it can't. Interpretation is everything. Also treating to bring everything within range will not work as a healing strategy.

These things often run in families.

 

[zrbarnes]

Just as an update, I finally got my labs done. I would post them here, but the formatting makes it hard to real. So here is a Google Doc Spreadsheet.

I'm a 26 year old, Caucasian male. 5'7", 140lbs. I'm moderately in shape. The blood was drawn after fasting for 12 hours.

From the tests, the only thing "out of range" is my LDL cholesterol, which is borderline high. Thanks dad for passing on those genes...

I'm not quite sure what else I'm looking for, other then the potassium looks fine, which is something I was a bit worried about because every blue moon I get muscle crampage that can be fixed by taking a couple potassium gluconate tablets.

Anyone can feel free to take a look and point out anything that I should investigate further (if you are bored and like to do such things, haha).

 

[richvank]

Hi, zr.

Your conventional lab test results look fine, but they don't address the vicious circle mechanism that ME/CFS and the autism spectrum share. If you want to get data on that, I suggest that you request the Health Diagnostics methylation pathways panel. Contact info is below. It requires an order from a physician or a chiropractor, and costs $295, including the mailer to send the blood samples to the lab. It won't matter that you have already started treatment that impacts the methylation cycle. You will still find out the current status of your methylation cycle, folate metabolism and glutathione. And you won't have to stop taking your supplements to get meaningful results from this panel.

Best regards,

Rich

Methylation Pathways Panel​

This panel will indicate whether a person has a partial methylation cycle block and/or glutathione depletion. I recommend that this panel be run before deciding whether to consider treatment for lifting the methylation cycle block. I am not associated with the lab that offers this panel.

The panel requires an order from a physician or a chiropractor. The best way to order the panel is by fax, on a clinician’s letterhead.


Available from:

Health Diagnostics and Research Institute540 Bordentown Avenue, Suite 2300
South Amboy, NJ 08879 USA
Phone: (732) 721-1234
Fax: (732) 525-3288

Email: lab@vitdiag.com

Lab Director: Elizabeth Valentine, M.D.

Dr. Tapan Audhya, Ph.D., is willing to help clinicians with interpretation of the panel by phone, or you can use the interpretive guide below:



March 25, 2012

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Interpretation of Results of the Methylation Pathways Panel​

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by​

Richard A. Van Konynenburg, Ph.D.​

Independent Researcher​

(richvank@aol.com)​

Disclaimer: The Methylation Pathways Panel is offered by the European Laboratory of Nutrients in the Netherlands and the Health Diagnostics and Research Institute in New Jersey, USA. I am not affiliated with these laboratories, but have been a user of this panel, and have written these suggestions at the request of Tapan Audhya, Ph.D., Director of Research for the Health Diagnostics lab, for the benefit of physicians who may not be familiar with this panel. My suggestions for the interpretation of results of the panel are based on my study of the biochemistry involved, on my own experience with interpreting panel results as part of the analysis of a fairly large number of cases of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) over the past four years, and on discussion of some of the issues with Dr. Audhya. I am a researcher, not a licensed physician. Treatment decisions based on the results of applying this panel and its interpretation to individual cases are the responsibility of the treating physician.

Application: In addition to being useful in analyzing cases of ME/CFS, this panel can also be usefully applied to cases of autism and other disorders that involve abnormalities in glutathione, methylation and the folate metabolism.

The panel includes measurement of two forms of glutathione (reduced and oxidized), S-adenosylmethionine (SAMe), S-adenosylhomocysteine (SAH), adenosine, and seven folate derivatives.

According to Dr. Audhya (personal communication), the reference ranges shown on the lab reports for each of these metabolites were derived from measurements on at least 120 healthy male and female volunteer medical students from ages 20 to 40, non-smoking, and with no known chronic diseases. The reference ranges extend to plus and minus two standard deviations from the mean of these measurements.

Glutathione (reduced): This is a measurement of the concentration of the
chemically reduced (active) form of glutathione (abbreviated GSH) in the blood
plasma. The reference range is 3.8 to 5.5 micromoles per liter.

Glutathione plays many important roles in the biochemistry of the body, including serving as the basis of the antioxidant enzyme system, participating in the detoxication system, and supporting the cell-mediated immune response, all of which exhibit deficits in CFS. The level of GSH in the plasma is likely to be more reflective of tissue intracellular glutathione status than the more commonly and more easily measured red blood cell or (essentially equivalent) whole blood glutathione level, which is about three orders of magnitude greater, because red blood cells are normally net producers of glutathione. Also, knowledge of the level of the reduced form, as distinguished from total (reduced plus oxidized) glutathione, which is more commonly measured, is more diagnostic of the status of glutathione function.

In order to be able to approximate the in vivo level of reduced glutathione when blood samples must be shipped to a lab, it is necessary to include special enzyme inhibitors in the sample vials, and these are included in the test kit supplied by these two laboratories.

Most people with chronic fatigue syndrome (PWCs), but not all, are found to have values of GSH that are below the reference range*. This means that they are suffering from glutathione depletion. As they undergo treatment to lift the partial methylation cycle block, this value usually rises into the normal range over a period of a few months. I believe that this is very important, because
glutathione normally participates in the intracellular metabolism of vitamin B12, and if it is low, a functional deficiency of vitamin B12 results, and insufficient methylcobalamin is produced to support methionine synthase in the methylation cycle. In my view, this is the mechanism that causes the onset of ME/CFS. This functional deficiency is not detected in a conventional serum B12 test, but will produce elevated methylmalonate in a urine organic acids test. In my opinion, many of the abnormalities and symptoms in ME/CFS can be traced directly to glutathione depletion.

Anecdotal evidence suggests that PWCs who do not have glutathione depletion do have abnormalities in the function of one or more of the enzymes that make use of glutathione, i.e. the glutathione peroxidases and/or glutathione transferases. This may be due to genetic polymorphisms or DNA adducts on the genes that code for these enzymes, or in the case of some of the glutathione peroxidases, to a low selenium status.

Glutathione (oxidized): This is a measurement of the concentration
of the oxidized form of glutathione (abbreviated GSSG) in the blood
plasma. The reference range is 0.16 to 0.50 micromoles per liter.

Normally, oxidized glutathione in the cells is recycled back to reduced glutathione by glutathione reductase, an enzyme that requires vitamin B2 and NADPH. If this reaction is overwhelmed by oxidative stress, the cells export excess GSSG to the plasma. In some (but not all) PWCs, GSSG is elevated above the normal
range, and this represents oxidative stress. It is more common in CFS to see this level in the high-normal range. This value may increase slightly under initial treatment of a partial methylation cycle block.*

Ratio of Glutatione (reduced) to Glutathione (oxidized): This is not shown explicitly on the panel results, but can be calculated from them. It is a measure of the redox potential in the plasma, and reflects the state of the antioxidant system in the cells. The normal mean value is 14. PWCs often have a value slightly more than half this amount, indicating a state of glutathione depletion and oxidative stress. This ratio has been found to increase during treatment of a partial methylation cycle block, but other types of treatment may be necessary to bring it to normal.*

S-adenosymethionine (RBC): This is a measure of the concentration of S-adenosylmethionine (SAMe) in the red blood cells. The reference range is 221 to 256 micromoles per deciliter.

SAMe is produced in the methylation cycle and is the main supplier of methyl (CH3) groups for a large number of methylation reactions in the body, including the methylation of DNA and the biosynthesis of creatine, carnitine, phosphatidylcholine, coenzyme Q10, melatonin and epinephrine. This measurement is made in the red blood cells because the level there reflects an average over a longer time and is less vulnerable to fluctuations than is the plasma level of SAMe.

Most PWCs have values below the reference range, and treatment raises the value.* A low value for SAMe represents a low methylation capacity, and
in CFS, it usually appears to result from an inhibition or partial block of the enzyme methionine synthase in the methylation cycle. Many of the abnormalities in CFS can be tied to lack of sufficient methylation capacity.

S-adenosylhomocysteine (RBC): This is a measure of the
concentration of S-adenosylhomocysteine (SAH) in the red blood cells. The reference range is 38.0 to 49.0 micromoles per deciliter.

SAH is the product of the many methyltransferase reactions that utilize SAMe as a source of methyl groups. In CFS, its value ranges from below the reference range to above the reference range. Values appear to converge toward the reference range with treatment.

Sum of SAM and SAH: When the sum of SAM and SAH is below about 268
micromoles per deciliter, it appears to suggest the presence of
upregulating polymorphisms in the cystathionine beta synthase (CBS)
enzyme, though this may not be true in every case. For those considering following the Yasko treatment program, this may be useful information.

Ratio of SAM to SAH: A ratio less than about 4.5 represents low
methylation capacity. Both the concentration of SAM and the ratio of
concentrations of SAM to SAH are important in determining the
methylation capacity, because they affect the rates of the methyltransferase reactions.

Adenosine: This is a measure of the concentration of adenosine in the
blood plasma. The reference range is 16.8 to 21.4 x 10(-8) molar.

Adenosine is a product of the reaction that converts SAH to homocysteine. It is also exported to the plasma when mitochondria develop a low energy charge, so that ATP drops down to ADP, AMP, and eventually, adenosine. Adenosine in the plasma is normally broken down to inosine by the enzyme adenosine deaminase.

In some PWCs adenosine is found to be high, in some it is low, and in some it is in the reference range. I don't yet understand what controls the adenosine level in these patients, and I suspect that there is more than one factor involved. In most PWCs who started with abnormal values, the adenosine level appears to be moving into the reference range with methylation cycle treatment, but more data are needed.

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.

If anyone finds errors in the above suggestions, I would appreciate being notified at richvank@aol.com.

* Nathan, N., and Van Konynenburg, R.A., Treatment Study of Methylation Cycle Support in Patients with Chronic Fatigue Syndrome and Fibromyalgia, poster paper, 9th International IACFS/ME Conference, Reno, Nevada, March 12-15, 2009. (http://www.mecfs-vic.org.au/sites/w...Article-2009VanKonynenburg-TrtMethylStudy.pdf)

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