I recently had the ELN (which is Health Diagnostics in the USA) methylation panel of tests. Just prior to that I'd had an NHS folate test. There seems to be a significant discrepency between the results. Hence I am wondering about the accuracy of the tests themselves, or the maybe the validity of the reference ranges or, perhaps more likely, my understanding of the relative measures.
Any and all insights would be appreciated.
History
My supplement regime was stable so there is no reason to believe they should be much different although the tests are at different times. The results were as follows:
NHS Folate
NHS Serum Folate >20 ng/ml (ref range 4.6-18.7)
ELN
The majority of these are outside the reference range with the folates being low. I calculated the sum of the folates tested by ELN to compare with the NHS total folate result. As some compounds are missing and as the test was not on the same day the result with the ELN numbers summing to about 65% of the 20ng/ml (which converts to 45 nmol/l using a molecular weight of 440) figure seems at least in the same ballpark. The confusing bit is that the NHS thinks I am above the 95% range while ELN thinks I am mainly below normal range although there are a couple of folate forms not tested for. In order for the NHS test to match the top of the ELN range it would have to be approximately triple the 20 ng/ml figure at 60 ng/ml. Why is this so? It seems that the ELN figures are widely relied upon but presumably the NHS has a much wider base of tests to determine a population distribution. The active folate (RBC) is 329 nmol/l. The UK average for men aged 19 to 64 years is 621 nmol/L (https://www.gov.uk/government/uploa..._data/file/414745/NDNS_Y1_4_Folate_report.pdf ). I am assuming these are the same measuring the same thing. It does seem something is wrong here either in me, the tests, the normal ranges or my interpretation.
Looking at Rich van Konynenburg's “Interpretation of Results of the Methylation Pathways Panel” interpretation it seems I am in methyl trap*. I am taking 5mg methylcobalamin/day, 1200 mcg methyl folate and 2.5g potassium bicarbonate (potassium chloride appears bad for bone density, see http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650509 ). Serum B12 tests high and serum potassium is mid range and supplementation has eliminated previous cramping. Rich doesn't address the high adenosine level however as the reaction S-Adenosylhomocysteine (SAH) → homocysteine + adenosine is reversible presumably this is helping to hold SAH high. This gives a poor S-Adenosylmethionine (SAM) / SAH ratio. Ben Lynch addresses adenosine in http://thequantifiedbody.net/ep-5-optimizing-methylation-dr-ben-lynch/ . That goes down another rabbit hole.
What I am primarily wondering is what I should take away from the above, in particular with regard to the folate levels. It seems that this should be a simple question of levels but these two tests seem to show different things.
Any thoughts would be appreciated.
Footnote:
Any and all insights would be appreciated.
History
My supplement regime was stable so there is no reason to believe they should be much different although the tests are at different times. The results were as follows:
NHS Folate
NHS Serum Folate >20 ng/ml (ref range 4.6-18.7)
ELN
The majority of these are outside the reference range with the folates being low. I calculated the sum of the folates tested by ELN to compare with the NHS total folate result. As some compounds are missing and as the test was not on the same day the result with the ELN numbers summing to about 65% of the 20ng/ml (which converts to 45 nmol/l using a molecular weight of 440) figure seems at least in the same ballpark. The confusing bit is that the NHS thinks I am above the 95% range while ELN thinks I am mainly below normal range although there are a couple of folate forms not tested for. In order for the NHS test to match the top of the ELN range it would have to be approximately triple the 20 ng/ml figure at 60 ng/ml. Why is this so? It seems that the ELN figures are widely relied upon but presumably the NHS has a much wider base of tests to determine a population distribution. The active folate (RBC) is 329 nmol/l. The UK average for men aged 19 to 64 years is 621 nmol/L (https://www.gov.uk/government/uploa..._data/file/414745/NDNS_Y1_4_Folate_report.pdf ). I am assuming these are the same measuring the same thing. It does seem something is wrong here either in me, the tests, the normal ranges or my interpretation.
Looking at Rich van Konynenburg's “Interpretation of Results of the Methylation Pathways Panel” interpretation it seems I am in methyl trap*. I am taking 5mg methylcobalamin/day, 1200 mcg methyl folate and 2.5g potassium bicarbonate (potassium chloride appears bad for bone density, see http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650509 ). Serum B12 tests high and serum potassium is mid range and supplementation has eliminated previous cramping. Rich doesn't address the high adenosine level however as the reaction S-Adenosylhomocysteine (SAH) → homocysteine + adenosine is reversible presumably this is helping to hold SAH high. This gives a poor S-Adenosylmethionine (SAM) / SAH ratio. Ben Lynch addresses adenosine in http://thequantifiedbody.net/ep-5-optimizing-methylation-dr-ben-lynch/ . That goes down another rabbit hole.
What I am primarily wondering is what I should take away from the above, in particular with regard to the folate levels. It seems that this should be a simple question of levels but these two tests seem to show different things.
Any thoughts would be appreciated.
Footnote:
* If the folate is ending up as methyl folate, why is that low? I finally found this post by Rich that addresses that question.
http://forums.phoenixrising.me/index.php?threads/are-there-any-doctors-who-will-interpret-the.18332/
“If the methyl trap mechanism were operating alone, it's true that the serum folate would rise. However, in ME/CFS, the serum folates are observed to be low. Prof. Marty Pall has convinced me that this is due to peroxynitrite reacting with methylfolate and breaking it down. There is published evidence for this reaction.”
http://forums.phoenixrising.me/index.php?threads/are-there-any-doctors-who-will-interpret-the.18332/
“If the methyl trap mechanism were operating alone, it's true that the serum folate would rise. However, in ME/CFS, the serum folates are observed to be low. Prof. Marty Pall has convinced me that this is due to peroxynitrite reacting with methylfolate and breaking it down. There is published evidence for this reaction.”
, to clarify I summed the serum folates which should give a like for like comparison. Maybe I am over analyzing it - the fact that NHS serum folate is much greater than the sum of the ELN serum folates worries me as to why. I cant get an NHS RBC folate so I cant compare anything with the ELN Active Folate (RBC) number. It looks as if I will just have to experiment with additional folate supplementation. As you say caledonia, from the ELN results folate looks low.