James says; "what are some causes and what should one do about low cystine and sulfate
levels in particular given slightly elevated homocysteine and mid range methionine?"
Well, if your methionine is mid range, then it would seem that your recycling
of homocysteine to methionine is adequate. Now you could quibble with that because there's
multiple things going in and out here. But my default position on this would be, you probably
don't have a problem recycling homocysteine to methionine. And that might explain why,
I'm assuming this is in the fasting state, your homocysteine is only slightly elevated. Now,
if you mean by slightly elevated, if you mean slightly elevated outside of the lab's reference
range, then that's very elevated. And so I would look at that a little bit differently,
but especially when paired with the low cystine and sulfate levels, it sounds like you have a low
rate of the transsulfuration pathway or the CBS enzyme, which is the first step in that pathway,
which takes homocysteine down to cysteine, which then can be metabolized to sulfate.
And if that's the case, you need to look at potential causes of that,
but the top ones would be... Well, actually, you know what... So the one that everyone
thinks about is vitamin B6, but I did a little bit of making some notes on some research. So
I know there's a couple other nutrients that are involved here. So let me pull up my notes...
Okay, so CBS, depends on heme iron, as well as vitamin B6. And it also uses serine,
which interconverts with glycine. So I would look at your serine and glycine levels,
because if those are low, they could be compromising
the CBS reaction. And I would look at your iron status and look at a CBC and make sure
your hemoglobin levels are normal. The heme iron in this enzyme is not the same as hemoglobin, but
they both depend on heme synthesis. And actually if you're running low in glycine,
that would compromise your heme synthesis as well. So it would be the case if you were low on B6,
and B6 itself is needed for the CBS reaction. So if you're low in glycine/B6,
you're probably going to be low in heme iron, even regardless of your iron status, just because of
compromising heme synthesis. So serine, glycine, iron, and B6 are all very big things to look at.
It is activated by S-adenosylmethionine. So even if your methionine is mid range, I will
look at your SAMe levels. So that would require getting the Genova Methylation Panel, which looks
at methionine and S-adenosylmethionine, because if that's blocked, then that could lead to poor
activation of CBS. Even if your heme iron, B6, serine, and glycine are all adequate.
And in that case, that would make me reinterpret the mid-range methionine levels. Because if your
S-adenosylmethionine conversion is blocked, then that should make your methionine levels high. And
so if they are mid-range, in that circumstance, I would change my interpretation away from recycling
of homocysteine to methionine is inadequate. And then I would then say, well, actually,
if they're only mid-range, despite the block in converting methionine to S-adenosylmethionine,
you must have poor recycling of homocysteine to methionine on top of everything else I just
said, because otherwise if you didn't, your methionine levels would be high.
So CBS converts homocysteine to cystathionine, and then the next enzyme, CGL, converts cystathionine
to cysteine and cysteine is the individual amino acid, cystine, which is what you had measured,
is the disulfide of that amino acid. So CGL
uses vitamin B6 again. Just vitamin B6. But
diabetes and methylglyoxal have been shown to be factors that decrease its expression and age
increases its expression. So I guess if you were a young diabetic, you would have
the worst CGL activity. Methylglyoxal is a whole big Pandora's box. So I want to leave it there
unless people have questions about that. But basically poor metabolic control
would compromise the conversion of cystathionine to cysteine. So if your cystine is low,
then you're probably looking at these two upstream enzymes, which are CBS and CGL. But if the sulfate
is similarly low as the cysteine, then there's probably no need for further explanation, because
sulfate is made from cysteine. But if the sulfate is a lot lower than the cysteine is,
then I would look at things even downstream from the cysteine. So CDO is the next enzyme that
oxidizes cysteine to cysteine sulfinic acid on the way to taurine and sulfate and CDO requires iron.
And then on the way to sulfate, you're going to come across sulfide, which requires molybdenum
to get to sulfate. So that was a lot. Let me see if I can summarize this.
So number one, look at whether methionine is being converted to SAMe.
If it's being converted to SAMe, well, then it's probably the case that your folate and B12
and choline recycling of homocysteine to methionine is fine. If it's not, then you probably
need to work on that. Although that's not going to explain the cystine and sulfate being low. If
that conversion is blocked, it being blocked could be driven by low magnesium, low ATP or genetics.
And you probably won't be able to activate the conversion of homocysteine to cysteine
and sulfate without fixing that. And if you can't fix that with magnesium and metabolic control and
improvement in ATP levels, then you are probably going to have to rely on SAMe supplementation.
And of course, if the SAMe is not blocked, then you don't need to worry about that.
Assuming you fix that, or it wasn't a problem in the first place then to get
homocysteine to cysteine and sulfate, you're looking at serine, glycine, vitamin B6, iron,
and molybdenum. All right. Thank you, James, for your question.