Kofi <k...@anon.un>

The FDA suspended manufacture of leucovorin (folinic acid) due to
quality issues in early March and since then, I've been off it and doing
rather poorly.  Supposedly production has resumed, but I've only been
able to get one bottle.  It's lasted about a week.  Since folinic acid
has become key in a number of chemotherapies, its availability may
remain limited for a while.

Now that I'm back on it, it's like somebody turned on the vitamin D
spigot again.  The results have been so dramatic it prompted me to dig
deeper.  It turns out regulatory T-cells have folic acid receptors [PMID
17613255] and certain autoimmune patients and low-functioning autistics
[PMID 18461502] generate autoantibodies against folic acid receptors -
quite possibly as the aftereffect of clearing out a viral infection or a
cancer that trained B-cells to target the receptor.

If these folic acid receptor antibodies are numerous enough, they can
block entry of folic acid into the central nervous system.  The receptor
is necessary for folic acid to cross the blood-brain barrier.  A patient
with normal serum folic acid levels might actually be deficient in the
CNS which would only show up in a tap - a procedure doctors rarely
perform.

It also turns out that low folic acid levels lead to higher vitamin D3
catabolism [PMID 19450178] so if the CNS is deficient in folic acid,
vitamin D3 isn't going to function properly - leading to a drop in redox
capacity (e.g., low glutathione)/metals detoxification/neurogenesis,
loss of antiviral functions/cathelicidin, increased cancer risk and
probably autoimmune issues as well.  But it's going to be invisible to
anybody checking strict serum levels.  It makes me wonder if certain
vital infections don't deliberately stir up anti-folic acid receptor
antibodies to block the antiviral effects of vitamin D3 within the
nervous system itself.

The upside, though, is that supplementing with folinic acid shots or a
high dose oral folic acid seems to restore CNS levels [PMID 19260931].  
Folic acid per se may stimulate Tregs even if patients don't have a
deficiency (which probably accounts for why tumors use folic acid and
are vulnerable to these antibodies).  This may mean folic acid is a good
general treatment for autoimmune disorders.

Serum folic acid in general can be affected by autoimmune diseases.  In
Celiac disease, the levels of transglutaminase antibodies seem inversely
correlated to serum folic acid levels [PMID 15861017, 17190764].  Given
how a serum drop would affect body-wide vitamin D3 levels and the
chemopreventative role of D3, this may be one reason bowel cancer risk
goes up in some of these autoimmune diseases.  Since estrogen helps
stimulate expression of the VDR, this may be a set of factors explaining
why bowel cancer is more common in men [PMID 19450178].

These folate receptor antibodies may be a cause of subfertility risk in
women [PMID 18950755].  They have been associated with high milk
consumption [PMID 19282368] and a milk-free diet can help reduce the
autoantibodies [PMID 18355335].  Given the role opioids play regulating
antibody production in B-cells [PMID 18387505], I have to wonder if this
cross-reaction to folate receptors caused by consuming cow's milk might
stem from the molecular similarities between the casein in milk and
opioids.

Given that my folinic acid supply will be sporadic for a while, does
anybody know where I can find an inexpensive, high dose folate
supplement - somewhere on the order of 10mg a day?