Re: Quick 25D, 1,25D question (but nerdy)

[Guest guest]

Tho it may have pathological consequences in some cases, I wouldnt call

the elevation of 1,25 in disease " dysregulation, " unless you believe it

obstructs pathogen clearance. If it does not obstruct clearance, then

it is simply up-regulated.

I dont get what youre saying about using it up? If you stop ingesting

25 I dont know how much will be lost via the 1,25 route (I may vaguely

recall that some 1,25 is converted right back into 25, some not) as

opposed to other routes such as excretion. But clearly the 25 is

gradually lost. It is very lipophilic and also present at

concentrations orders of magnitude higher than that of 1,25 - therefore

levels take a long time to go down when you cease to ingest it. Also

one or both of the species can be synthed by the skin using light, I

forget which one(s).

> As I start to take a gander at this literature, one (quick) question

comes to mind: If

> 1,25D is over-regulated by macrophages (e.g., not the usual 25D->

1,25D kidney

> stuff), that WOULDN'T per se require a concommitant drop in 25D

(the " using it up "

> hypothesis). Thus, 1,25D dysregulation from inflammation would exist

independent

> of any 25D deficiency. In contrast, LOW 25D and HIGH 1,25D would

implicate a

> deficiency vs a immune dysregulation, no?

[Guest guest]

Here's what I'm saying:

You don't need a decrease in 25D to account for an increase in 1,25 D. Instead,

a

DECREASE in the ENZYME that eats up 1,25 D could also yield high 1,25D. Thus,

one

could get high 1,25D in the ABSENCE of lower 25 D. And indeed that is what the

Vidals paper you refered me to seems to be saying.

Upregulation, downregulation are specific instances of dysregulation, doesn't

matter

the effects.

> > As I start to take a gander at this literature, one (quick) question

> comes to mind: If

> > 1,25D is over-regulated by macrophages (e.g., not the usual 25D->

> 1,25D kidney

> > stuff), that WOULDN'T per se require a concommitant drop in 25D

> (the " using it up "

> > hypothesis). Thus, 1,25D dysregulation from inflammation would exist

> independent

> > of any 25D deficiency. In contrast, LOW 25D and HIGH 1,25D would

> implicate a

> > deficiency vs a immune dysregulation, no?

[Guest guest]

" Dys " means bad and bad can only be relative to a goal - in this case

the goal of squooshing our gross lil enemies. The upregulation of

serum (and paracrine) 1,25d could be eufunctional during infection

just as upregulation of serum adrenaline is eufunctional during a

gunfight. Its not just semantics to me, since to me " dys " immediately

suggests that we ought to intentionally modulate (fix) our 1,25d

levels in order to beat bacteria, which I am not at all convinced is

correct.

Thanks for the clarification on the other thing; I now see what you

mean: that reducing expression of 1,25d catabolizing enzymes could

increase 1,25d levels *without* changing the rate at which 25d is

converted to 1,25d. That is a good point. Are you saying that this

pattern, which clearly is a biological possibility, happens in fact?

Dont feel obliged to study/reply re that question on my account if

youre not personally interested in it, since D is not a huge interest

for me personally.

> > > As I start to take a gander at this literature, one (quick)

question

> > comes to mind: If

> > > 1,25D is over-regulated by macrophages (e.g., not the usual 25D-

>

> > 1,25D kidney

> > > stuff), that WOULDN'T per se require a concommitant drop in 25D

> > (the " using it up "

> > > hypothesis). Thus, 1,25D dysregulation from inflammation would

exist

> > independent

> > > of any 25D deficiency. In contrast, LOW 25D and HIGH 1,25D

would

> > implicate a

> > > deficiency vs a immune dysregulation, no?