You say you don't see any circumstance for supplementing with more than 1mg folate per day. However, I saw the below case study where a patient was homozygous for a pathogenic variant in SLC191A, and their issues were improved by supplementing with 10mg/day folic acid despite normal levels of serum folate.
I've seen another case study in infants with SLA19A1 mutations where they supplemented them with 2.5mg/day to improve their health.
I'm heterozygous for rs1555874527 in SLC19A1/COL18A which is deemed pathogenic and rare (freq 0.00001556). I also have borderline high MCV (98.5) which has been increasing and symptoms of anemia and anxiety.
Do you think it would be wise to supplement with folinic acid in the range of 2.4mg/day (0.8mg at each meal)? At least until symptoms have improved, then dial back a bit?
If so, would you advise supplementation of other nutrients to prevent imbalances?
Just did some research, and yes, it looks like this variant is more likely to affect COL18A1 instead of SLC19A1. Thanks for this input. Didn't know about the different types of mutations (frameshift vs intron) and the likelihood that they cause problems.
Looking forward to going through BioOpt when I get to the front of the line!
I understand that you support continuing supplements before functional testing, and I do the same with my patients. However, I’m curious about your thoughts on B6 supplementation before testing. Some of my patients are on a methylated multivitamin containing 75 mg of Vitamin B6 (as pyridoxine HCl and pyridoxal 5'-phosphate), and their fasting B6 levels often come back significantly elevated—sometimes double the upper limit. This causes concern for them. What are your thoughts on this?
In general I don't think elevated B6 is useful as a marker of neuropathy. The presence of neuropathy is useful as a marker of neuropathy. If they stop the supplement for a week and the level is normal, what insight did you gain?
I will try that and see what comes up having them remove supplements for a week before testing. I understand that pyridoxine HCl has a much shorter half life than pyridoxal 5'-phosphate (hours vs weeks). I guess that if the levels come back to normal in a week, then their p5p clearance is working pretty fast and that I would need to reduce their P5P daily intake. What do you think?
From CheatSheet 3: 'Free copper index: subtract (ceruloplasmin * 3.15 in mcg/L) from serum copper in mcg/L. This is the free copper. Divide this by the serum copper to yield the % free copper. If free copper is above 15 or the % free copper is above 15%, see Elevated Free Copper below.'
My ceruloplasmin is 19.3 mg/dL and serum copper is 13.2 µmol/L;
Conversion: ceruloplasmin 193,000 µg/L; serum copper 838.8072 µg/L; I used unitslab.com for conversion of copper.
If someone wants to get their nutrients tested but is on a feeding tube for part of their nutrition, would the vitamins added to the formula impact lab test results?
Hi Chris, Multiple times in your cheat sheet you recommend the Genova ION + 40 Amino Acids test (test #3102). Going to the provided link at https://www.gdx.net/nutrition, I don't see that test anywhere!
Has it been discontinued? If so, what test(s) do you recommend instead? I was about to order one.
Chris, I believe you used to live in New York & are likely familiar with the legal limitations around Genova testing in this state. Do you have any recommendations for how a New Yorker could get a blood draw for the NutrEval, i.e. via a physician in New Jersey or Connecticut, potentially?
Hi Dr CMJ,
You say you don't see any circumstance for supplementing with more than 1mg folate per day. However, I saw the below case study where a patient was homozygous for a pathogenic variant in SLC191A, and their issues were improved by supplementing with 10mg/day folic acid despite normal levels of serum folate.
https://pmc.ncbi.nlm.nih.gov/articles/PMC7330012/
I've seen another case study in infants with SLA19A1 mutations where they supplemented them with 2.5mg/day to improve their health.
I'm heterozygous for rs1555874527 in SLC19A1/COL18A which is deemed pathogenic and rare (freq 0.00001556). I also have borderline high MCV (98.5) which has been increasing and symptoms of anemia and anxiety.
Do you think it would be wise to supplement with folinic acid in the range of 2.4mg/day (0.8mg at each meal)? At least until symptoms have improved, then dial back a bit?
If so, would you advise supplementation of other nutrients to prevent imbalances?
I was speaking generally, I do think with a deletion of a folate transporter higher doses could be tried and judged on their results.
According to dbSNP rs1555874527 is not reported in ClinVar and is an intron variant in SLC19A1.
Not sure where you get pathogenicity from. But it could be pathogenic. Nevertheless I would judge that by serum to cellular folate ratio on Vibrant.
I would use low cellular folate on Vibrant to justify a trial with higher doses of folate.
Vibrant results were
Serum folate High: >20ng/mL
RBC folate Low: 108ng/mL (just barely in reference range on low end)
As for rs1555874527, Genome Explorer on sequencing.com labeled it as Pathogenic.
Maybe it's pathogenic in the COL18A1 (frameshift) gene and not pathogenic in SLC19A1 (intron)?
Thanks for the response.
Just did some research, and yes, it looks like this variant is more likely to affect COL18A1 instead of SLC19A1. Thanks for this input. Didn't know about the different types of mutations (frameshift vs intron) and the likelihood that they cause problems.
Looking forward to going through BioOpt when I get to the front of the line!
As far as I can tell, Sequencing uses some proprietary rating system and I can't make heads or tails out of it.
High serum folate and low RBC folate is consistent with impaired transport. It could also be due to a recent increase in folate intake.
I understand that you support continuing supplements before functional testing, and I do the same with my patients. However, I’m curious about your thoughts on B6 supplementation before testing. Some of my patients are on a methylated multivitamin containing 75 mg of Vitamin B6 (as pyridoxine HCl and pyridoxal 5'-phosphate), and their fasting B6 levels often come back significantly elevated—sometimes double the upper limit. This causes concern for them. What are your thoughts on this?
In general I don't think elevated B6 is useful as a marker of neuropathy. The presence of neuropathy is useful as a marker of neuropathy. If they stop the supplement for a week and the level is normal, what insight did you gain?
I will try that and see what comes up having them remove supplements for a week before testing. I understand that pyridoxine HCl has a much shorter half life than pyridoxal 5'-phosphate (hours vs weeks). I guess that if the levels come back to normal in a week, then their p5p clearance is working pretty fast and that I would need to reduce their P5P daily intake. What do you think?
I would think if reducing P5P resolved neuropathy, the P5P was the cause of the neuropathy, and the testing is a waste of time.
Hi Chris,
From CheatSheet 3: 'Free copper index: subtract (ceruloplasmin * 3.15 in mcg/L) from serum copper in mcg/L. This is the free copper. Divide this by the serum copper to yield the % free copper. If free copper is above 15 or the % free copper is above 15%, see Elevated Free Copper below.'
My ceruloplasmin is 19.3 mg/dL and serum copper is 13.2 µmol/L;
Conversion: ceruloplasmin 193,000 µg/L; serum copper 838.8072 µg/L; I used unitslab.com for conversion of copper.
Calc: 19.3 µg/L x 3.15 = 607950 µg/L;
838.8072 µg/L - 607950 µg/L= -607,111.1928 µg/L -> free copper
-607,111.1928 µg/L : 838.8072 µg/L = ~ -723,78 %
This makes no sense - but I can't find the mistake
free copper as calculated by the lab is 2.87 µmol/L
If someone wants to get their nutrients tested but is on a feeding tube for part of their nutrition, would the vitamins added to the formula impact lab test results?
Some of them, but not in a way that makes testing not useful.
Hi Chris, Multiple times in your cheat sheet you recommend the Genova ION + 40 Amino Acids test (test #3102). Going to the provided link at https://www.gdx.net/nutrition, I don't see that test anywhere!
Has it been discontinued? If so, what test(s) do you recommend instead? I was about to order one.
thanks.
Doctors can order it inside their portal and DTC companies like truehealthlabs should allow you to order it. If all else fails get the NutrEval.
Chris, I believe you used to live in New York & are likely familiar with the legal limitations around Genova testing in this state. Do you have any recommendations for how a New Yorker could get a blood draw for the NutrEval, i.e. via a physician in New Jersey or Connecticut, potentially?