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Rich, and all: Lab Results: High b12, low RBC folate, "low-normal" MMA...???

dannybex

Senior Member
Messages
3,561
Location
Seattle
Hello,

Got some new lab tests done, quite comprehensive for a medicaid-based doc, but have a couple of questions.

My b12 was high (Labcorp's range stops at "1999", and my result was ">1999". It doesn't of course say what form of b12. I was taking b12 shots, usually 3-4 times a week (with some gaps too) for the last 4-5 months.

RBC folate was low, which I guess isn't a surprise, but kind of nice to see validated on a medicaid panel. It was 435. Their range is 468-1258. I wasn't taking too much methylfolate, as I wasn't sure if it was causing havoc or not. I don't think it was, because there were some days when I took it for 2-3 days (in small amounts) and felt a little stronger, and more hopeful -- but not sure, so I didn't take it regularily.

The odd result was that my urinary MMA was 'low-normal' at 3.7 (the normal range for labcorp is 1.6 - 29.7). They also listed a "MMA-Normalized" result of 1.0, with the normal range being 0.4 - 2.5 -- I'm not sure what that means. But I had to convince her the MMA test was critical, so now that it's 'normal' she's suggesting I need to stop the b12 (which I did 2-3 weeks back), and increase my folate. (She was always skeptical of the b12 issue, but I finally brought in studies from journals she accepts.)

SO...questions:

Does too much b12 lower folate levels?

Or...do you think this is mainly due to not getting enough folate regularily the past year? (My methylation panel had low folates as well.)

If I increase the folate, which I'm starting to do with small amounts of folinic (then will start methylfolate in a couple weeks), would it be prudent to do a b12 shot say once a week?

Not sure what to make of the MMA situation.

THANK YOU,

Dan

p.s. Still lots of anxiety, stress intolerance, but another specialist I'm working with says that's due to erratically high-ish (then low AM) cortisol -- adrenal burnout.
 

richvank

Senior Member
Messages
2,732
***Hi, Dan.

***My responses are at the asterisks below:


Hello,

Got some new lab tests done, quite comprehensive for a medicaid-based doc, but have a couple of questions.

My b12 was high (Labcorp's range stops at "1999", and my result was ">1999". It doesn't of course say what form of b12. I was taking b12 shots, usually 3-4 times a week (with some gaps too) for the last 4-5 months.

***Serum B12 consists mostly of B12 bound to haptocorrin. This fraction is not directly available to the cells in general, but is slowly picked up by the liver cells. It is partly stored in the liver and partly excreted in the bile to the gut, where it has an opportunity to be reabsorbed and put back into the blood, bound to transcobalamin, which is available to the cells in general. A high serum B12 level shows that you do not have an absolute B12 deficiency (which you shouldn't of course, having had all those shots). However, it does not tell you whether or not you have a functional B12 deficiency.

RBC folate was low, which I guess isn't a surprise, but kind of nice to see validated on a medicaid panel. It was 435. Their range is 468-1258.

***A low RBC folate measurement suggests that you have oxidative stress, which has damaged the cell membranes so that some of the folate that was in the RBCs when they were originally produced has leaked out.

I wasn't taking too much methylfolate, as I wasn't sure if it was causing havoc or not. I don't think it was, because there were some days when I took it for 2-3 days (in small amounts) and felt a little stronger, and more hopeful -- but not sure, so I didn't take it regularily.

The odd result was that my urinary MMA was 'low-normal' at 3.7 (the normal range for labcorp is 1.6 - 29.7). They also listed a "MMA-Normalized" result of 1.0, with the normal range being 0.4 - 2.5 -- I'm not sure what that means.

***It probably means the MMA concentration divided by the creatinine concentration in the urine. This compensates for varying amounts of dilution of the urine by water, on the assumption that the creatinine excretion is more or less constant for everyone, depending only on lean body mass. I don't think this is correct in ME/CFS, because creatine, its precursor, requires methylation, which is not normal in ME/CFS. But either way, your MMA value came out normal. This is used as an indicator of the level of adenosylcobalamin, which is needed to metabolize MMA. If MMA is low, it is often inferred that there is not either an absolute or a functional deficiency of B12. This is usually true, but there can be complications with this marker. For example, if there is a severe B6 deficiency, MMA could be low when there is still a problem with B12 function.

But I had to convince her the MMA test was critical, so now that it's 'normal' she's suggesting I need to stop the b12 (which I did 2-3 weeks back), and increase my folate. (She was always skeptical of the b12 issue, but I finally brought in studies from journals she accepts.)

SO...questions:

Does too much b12 lower folate levels?

***No. In fact, if B12 goes too low, folate will be lost from the cells.

Or...do you think this is mainly due to not getting enough folate regularily the past year? (My methylation panel had low folates as well.)

***The methylation panel has more reliable folate measures. It's difficult to conclude much from the RBC folate measurement, except the likely presence of oxidative stress.

If I increase the folate, which I'm starting to do with small amounts of folinic (then will start methylfolate in a couple weeks), would it be prudent to do a b12 shot say once a week?

***It's probably best to do something like that, because if you do have a functional B12 deficiency, the demand for B12 may increase as you bring folate up.

Not sure what to make of the MMA situation.

THANK YOU,

Dan

p.s. Still lots of anxiety, stress intolerance, but another specialist I'm working with says that's due to erratically high-ish (then low AM) cortisol -- adrenal burnout.

***As you probably know, I have suggested that in ME/CFS this is usually due to abnormal secretion of ACTH, because of glutathione depletion in the pituitary. If your glutathione is depleted, and you are able to bring it up by lifting the partial methylation cycle block, your diurnal cortisol variation should become more normal.

***I hope this helps.

***Best regards,

***Rich
 

merylg

Senior Member
Messages
841
Location
Sydney, NSW, Australia
Hi Dan & Rich,

I am working my way through some similar issues regarding B12 & folate!

Rich, I have a question regarding where to get testing in Australia relevant to the Methylation Pathway?
Here is one place accessible to Australians for Functional Pathology Testing:

http://healthscopepathology.com.au/html/functionalPathology/fpTests.shtml

Can you please tell me if any of these tests would give enough useful information re Methylation?

Thanks Rich,

meryl (I have no financial interest in this company)
 

dannybex

Senior Member
Messages
3,561
Location
Seattle
Thanks Rich! :)

Yes, very helpful as always -- thanks so much!

I don't know if this helps clarify things any better, but my BUN was 19, and the BUN/Creatinine ratio was considered high at 28 (the norm: 9-20), and my serum creatinine was low at 0.69, I guess because of the partial methylation block.

And yes, while not officially tested, I'm assuming my b6 is low as I had very poor dream recall until lately, which is improving from time to time. I wasn't able to tolerate it earlier this year, but have been able to increase it to about 10-20 mgs a day, provided I take some riboflavin (and magnesium) at the same time. The riboflavin seems to help reduce the tingling/neuropathy that would happen with the b6.

So anyway, thank you so much Rich -- very helpful.

Dan
 

richvank

Senior Member
Messages
2,732
Yes, very helpful as always -- thanks so much!

I don't know if this helps clarify things any better, but my BUN was 19, and the BUN/Creatinine ratio was considered high at 28 (the norm: 9-20), and my serum creatinine was low at 0.69, I guess because of the partial methylation block.

And yes, while not officially tested, I'm assuming my b6 is low as I had very poor dream recall until lately, which is improving from time to time. I wasn't able to tolerate it earlier this year, but have been able to increase it to about 10-20 mgs a day, provided I take some riboflavin (and magnesium) at the same time. The riboflavin seems to help reduce the tingling/neuropathy that would happen with the b6.

So anyway, thank you so much Rich -- very helpful.

Dan

Hi, Dan.

That all makes sense to me. Your creatine production may be low because of a methylation deficit that that would raise the BUN/creatinine ratio. B6 is needed to synthesize neurotransmitters, and B2 is needed to help break them down, so a balance between the two is necessary to maintain normal neurotransmitter levels.

Best regards,

Rich
 

richvank

Senior Member
Messages
2,732
Hi Dan & Rich,

I am working my way through some similar issues regarding B12 & folate!

Rich, I have a question regarding where to get testing in Australia relevant to the Methylation Pathway?
Here is one place accessible to Australians for Functional Pathology Testing:

http://healthscopepathology.com.au/html/functionalPathology/fpTests.shtml

Can you please tell me if any of these tests would give enough useful information re Methylation?

Thanks Rich,

meryl (I have no financial interest in this company)


Hi, meryl.

The urine organic acids panel, together with the urine amino acids panel, will give indirect information on the status of methylation. In the urine organic acids panel, if the methylmalonic acid and the formiminoglutamic acid are both elevated, that is usually a good indication of a partial methylation cycle block. If pyroglutamic acid is high or low on this panel, it indicates glutathione depletion. If there is a large drop between citric acid and either of the next two citric acid metabolites, that also suggests glutathione depletion. On the amino acids panel, the sulfur-containing amino acids (methionine, cystathionine, cysteine, cystine and taurine) will give information about the status of the sulfur metabolism in general, and glycine, serine and sarcosine will give information about the methylation cycle and the transsulfuration pathway.

Best regards,

Rich
 

merylg

Senior Member
Messages
841
Location
Sydney, NSW, Australia
Hi, meryl.

The urine organic acids panel, together with the urine amino acids panel, will give indirect information on the status of methylation. In the urine organic acids panel, if the methylmalonic acid and the formiminoglutamic acid are both elevated, that is usually a good indication of a partial methylation cycle block. If pyroglutamic acid is high or low on this panel, it indicates glutathione depletion. If there is a large drop between citric acid and either of the next two citric acid metabolites, that also suggests glutathione depletion. On the amino acids panel, the sulfur-containing amino acids (methionine, cystathionine, cysteine, cystine and taurine) will give information about the status of the sulfur metabolism in general, and glycine, serine and sarcosine will give information about the methylation cycle and the transsulfuration pathway.

Best regards,

Rich

Hi Rich, thanks for your reply. It would have been good to have some baseline (and I think you did mention this) before I started on a Methylation Protocol & a whole bunch of other supplements...but for whatever reason it didn't happen.

I've been on a Methylation Protocol now for about 7 months. Plus I take some extra supplements. If I were to have the tests discussed above, wouldn't the supplements interfere with the interpretation??? For example I take N-Acetyl Cysteine, Reduced Glutathione and L-Serine.

Would I have to cease some of these extras before having the tests? I'm confused :confused: and that's not unusual!

By the way, I have improved from bed-bound earlier this year (after major CFS, ME, FM, MCS - type crash) to being mostly housebound. Am able to get out for about 1/2 day once a week. Still able to drive short distances from home.

Thanks Rich, once again appreciate your input :thumbsup:

meryl
 

richvank

Senior Member
Messages
2,732
Hi Rich, thanks for your reply. It would have been good to have some baseline (and I think you did mention this) before I started on a Methylation Protocol & a whole bunch of other supplements...but for whatever reason it didn't happen.

I've been on a Methylation Protocol now for about 7 months. Plus I take some extra supplements. If I were to have the tests discussed above, wouldn't the supplements interfere with the interpretation??? For example I take N-Acetyl Cysteine, Reduced Glutathione and L-Serine.

Would I have to cease some of these extras before having the tests? I'm confused :confused: and that's not unusual!

By the way, I have improved from bed-bound earlier this year (after major CFS, ME, FM, MCS - type crash) to being mostly housebound. Am able to get out for about 1/2 day once a week. Still able to drive short distances from home.

Thanks Rich, once again appreciate your input :thumbsup:

meryl

Hi, meryl.

I'm glad to hear about the improvement you have experienced.

Yes, the supplements you mentioned could influence the results of the lab tests I described. The tests come with instructions as to what should be discontinued and for how long. That can be helpful for comparing your results to the results of others, which are reflected in the lab's reference ranges. However, if discontinuing the supplements would cause a significant worsening of a person's condition, my view is that they should be continued, and it should be recorded what the supplements and dosages are, to assist in the interpretation of the results.

I usually advocate running the Methylation Pathways Panel that is offered by the European Laboratory of Nutrients in the Netherlands, and the Health Diagnostics and Research Institute in New Jersey, USA. I realize that this takes special FedEx shipping on ice (ordinary water ice) from Australia, and can only be done from some of the larger cities (including Sydney), but I have heard of people in Australia successfully sending samples to both these labs. The Methylation Pathways Panel gives direct information about the methylation cycle, the folate metabolism, and glutathione, and it is not very sensitive to supplements. In our clinical study, the women continued to take the supplements in the simplified protocol as they were retested with this panel, and the results came out smoothly improving over time.

Best regards,

Rich
 

merylg

Senior Member
Messages
841
Location
Sydney, NSW, Australia
Hi, meryl.

I'm glad to hear about the improvement you have experienced.

Yes, the supplements you mentioned could influence the results of the lab tests I described. The tests come with instructions as to what should be discontinued and for how long. That can be helpful for comparing your results to the results of others, which are reflected in the lab's reference ranges. However, if discontinuing the supplements would cause a significant worsening of a person's condition, my view is that they should be continued, and it should be recorded what the supplements and dosages are, to assist in the interpretation of the results.

I usually advocate running the Methylation Pathways Panel that is offered by the European Laboratory of Nutrients in the Netherlands, and the Health Diagnostics and Research Institute in New Jersey, USA. I realize that this takes special FedEx shipping on ice (ordinary water ice) from Australia, and can only be done from some of the larger cities (including Sydney), but I have heard of people in Australia successfully sending samples to both these labs. The Methylation Pathways Panel gives direct information about the methylation cycle, the folate metabolism, and glutathione, and it is not very sensitive to supplements. In our clinical study, the women continued to take the supplements in the simplified protocol as they were retested with this panel, and the results came out smoothly improving over time.

Best regards,

Rich

Thanks Rich. You have given me lots to think about for the New Year!

Regards,

meryl