Psoriasis support - Folic acid supplements challenged

Author

Folic acid supplements challenged - L-methylfolate better?

Cruiser

2005-09-24, 1:34 pm

There is a small discussion going on, over at the sci.life-extension group,
about the bioavailability of folic acid supplements.

This appears similar to the questions I raised about the cyanocobalamin
supplements, but without the cyanide poisoning issue.

I switched to methylcobalamin sublingual. Now I am wondering about the folic
acid supplement that I am using.

It is the same deal. The active form in the body for B12 is methylcobalamin
and now they are saying that the active form of folic acid in the body is
L-methylfolate. In both cases, the body's ability to convert the regular
supplement to the methylated form is being questioned.

http://www.hsfolate.com/folate_not_folic.htm
http://store.yahoo.com/iherb/metafolin.html

Cruiser

Cruiser

2005-09-24, 1:34 pm

Here is more information.

It looks like Merck released this product in 2001 and there has been slow
market uptake by supplement makers.

Most of the products using it are mixes of supplements and not straight
metafolin. Most of those products contain cyanocobalamin, which I get in my
regular vitamin supplements. Unfortunately, if I want a couple pills that
provide a host of nutrients, I have to put up with it. However, I don't
want anymore of that crap in me than I already get.

From what I am reading regular folic acid supplement may not be very usable
and may inhibit absorption of usable methyfolate from dietary sources.

As a side note, I started eating crab and seafood delis from Subway, for
lunch a few years ago, and I found that psoriasis reduced considerably. I
attributed this change to other things that I was doing. I would get a heap
of lettuce every day, and often drank a V8 juice, which is made with leafy
green vegetables. I was eating more salads at the time. I am not fond of
salad and rarely eat it. I wonder if folic acid has been the chemical
process limiter for me, in reducing homocysteine levels. When I stopped
eating at subway and also strayed from eating salads, the psoriasis stopped
improving, and it has even started to get worse lately.

I have supplemented all this time with folic acid in adequate amounts, but I
am beginning to believe that folic acid supplements are not well utilized in
the body. I am trying to source some Source Naturals metafolin supplement,
but it does not seem to be available at any of the health stores around.

I can get it from the WEB, but that will take weeks.

http://www.metafolin.com/
http://www.metafolin.com/pdfs/metafolin2004_merck.pdf

I started drinking a 340ml can of V8 juice at lunch, a couple weeks ago, and
I have sent a note to Campbell, requesting information on the methyfolate
content of a can of V8. It is made with the juice of leafy green vegetables,
and should contain at least some folate.

Maybe, I should start gobbling spinach and orange juice.

Hmmmm.....

Cruiser

cruiser

2005-09-24, 1:34 pm

http://www.emedicine.com/med/topic8...#section~workup

Just found a very good reference on Folic Acid. Tons of really good
information.

Here is a sampling.

polyglutamate - form in food
monglutamate - in plasma, the only form that can pass membranes
tetrahydrofolic acid (THFA) - active form in body
500-20,000 mcg of folate in body stores

Within the plasma, folate is present, mostly in the 5-methyltetrahydrofolate
(5-methyl THFA) form, and is loosely associated with plasma albumin in
circulation. The 5-methyl THFA enters the cell via a diverse range of folate
transporters with differing affinities and mechanisms (ie, adenosine
triphosphate [ATP]-dependent H+ cotransporter or anion exchanger). Once
inside, 5-methyl THFA may be demethylated to THFA, the active form
participating in folate-dependent enzymatic reactions. Cobalamin (B-12) is
required in this conversion, and in its absence, folate is "trapped" as
5-methyl THFA.

From then on, folate no longer is able to participate in its metabolic
pathways, and megaloblastic anemia results. Large doses of supplemental
folate can bypass the folate trap, and megaloblastic anemia will not occur.
However, the neurologic/psychiatric abnormalities associated with B-12
deficiency ensue progressively.

The biologically active form of folic acid is tetrahydrofolic acid (THFA),
which is derived by the 2-step reduction of folate involving dihydrofolate
reductase. THFA plays a key role in the transfer of 1-carbon units (such as
methyl, methylene, and formyl groups) to the essential substrates involved
in the synthesis of DNA, RNA, and proteins. More specifically, THFA is
involved with the enzymatic reactions necessary to synthesis of purine,
thymidine, and amino acid. Manifestations of folate deficiency thereafter,
not surprisingly, would involve impairment of cell division, accumulation of
possibly toxic metabolites such as homocysteine, and impairment of
methylation reactions involved in the regulation of gene expression, thus
increasing neoplastic risks.
---snip--
Mechanistically speaking, current theory proposes that folate is essential
for synthesis of S-adenosylmethionine, which is involved in numerous
methylation reactions. This methylation process is central to the
biochemical basis of proper neuropsychiatric functioning.
---snip---
People with alcoholism can have very active alcohol dehydrogenase that binds
up folate and thus interferes with folate with folate utilization.
---snip----
Increased requirement: Factors that increase the metabolic rate can increase
the folic requirement. Infancy (a period of rapid growth), pregnancy (rapid
fetal growth), lactation (uptake of folate into breast milk), malignancy
(increased cell turnover), concurrent infection (immunoproliferative
response), and chronic hemolytic anemia (increased hematopoiesis) all can
result in an increased folate requirement.
---snip---
Increased excretion/loss: Increased excretion of folate can occur subsequent
to vitamin B-12 deficiency. During the course of vitamin B-12 deficiency,
methylene THFA is known to accumulate in the serum, which is known as the
folate trap phenomenon. In turn, large amounts of folate filter through the
glomerulus, and urine excretion occurs. Another mechanism of excess
excretion occurs in people with chronic alcoholism who can have increased
excretion of folate into the bile. Patients undergoing hemodialysis also
have been known to have excess folate loss during procedures.
---snip---
Increased destruction: Superoxide, an active metabolite of ethanol
metabolism, is known to inactivate folate by splitting the folate molecule
in half between the C9 and N10 position. The relationship between cigarette
smoking and low folate levels has been noted as possibly due to folate
inactivation in exposed tissue.
---snip---
resistance to treatment may occur in patients with alcoholism and
deficiencies of other vitamins; adverse effects include anorexia, nausea,
abdominal pain, flatulence, altered sleep pattern, irritability,
overactivity, erythremia, rash, and itching.

Cruiser

randall

2005-09-24, 1:34 pm

Hi,

Ok as to your list of things that folate is good for. Good info to make
one think.

Let's try to get a clearer picture via pubmed of the role of P and
folic acid.

Here's the first hit, that speaks to me. The majority of hits of course
are for
MTX and folic acid as mtx inhibits it.

http://www.ncbi.nlm.nih.gov/entrez/...st_uids=9420019

Folate and antifolate pharmacology.

Kamen B.

Department of Pediatrics, The university of Texas Southwestern Medical
Center, Dallas 75235-9063, USA.

Folic acid is a water-soluble vitamin associated with the other B
vitamins. In its fully reduced form (tetrahydrofolate), folate serves
as a 1-carbon donor for synthesis of purines and thymidine as well as
in the remethylation cycle of homocysteine to methionine. Folate is
essential for normal cell growth and replication. It therefore is not
surprising that folate analogues have served and continue to serve well
as antibiotics and cytotoxic drugs in the treatment of cancer,
autoimmune diseases, psoriasis, and bacterial and protozoal infections.
During the past 50 years, many of the enzymes requiring folate as a
co-factor (ie, thymidylate synthase), and molecules critical in folate
homeostasis (ie, the reduced folate carrier, folylpolyglutamate
synthase), have been purified and even crystallized. The genes have
been cloned, sequenced, and mapped, providing detailed knowledge of
their regulation and three-dimensional structure. This has, in part,
led to the rational synthesis of a large number of folate analogues
that differ from methotrexate, the "classical antifolate," in
transport, metabolism, and intracellular targets. Currently, several
new folate analogues with unique biochemical properties and clinical
applications are being tested. The goals of this brief review are to
review folate homeostasis, to highlight the similarities and
differences between natural folate and antifolates with respect to
biochemistry and metabolism, and to present the pharmacology of
methotrexate and several next-generation folate analogues, such as
trimetrexate and raltritrexed, with an emphasis on mechanisms of drug
resistance.

PMID: 9420019

The major theme on the P group also seems to be the anti folic acid
MTX,
http://groups.google.com/groups?q=f...sis&qt_s=Search

Next, look what else is on that list now.

The antifolate activity of tea catechins.

Navarro-Peran E, Cabezas-Herrera J, Garcia-Canovas F, Durrant MC,
Thorneley RN, Rodriguez-Lopez JN.

Grupo de Investigacion de Enzimologia, Departamento de Bioquimica y
Biologia Molecular A, Facultad de Biologia, Universidad de Murcia,
Spain.

A naturally occurring gallated polyphenol isolated from green tea
leaves, (-)-epigallocatechin gallate (EGCG), has been shown to be an
inhibitor of dihydrofolate reductase (DHFR) activity in vitro at
concentrations found in the serum and tissues of green tea drinkers
(0.1-1.0 micromol/L). These data provide the first evidence that the
prophylactic effect of green tea drinking on certain forms of cancer,
suggested by epidemiologic studies, is due to the inhibition of DHFR by
EGCG and could also explain why tea extracts have been traditionally
used in "alternative medicine" as anticarcinogenic/antibiotic agents or
in the treatment of conditions such as psoriasis. EGCG exhibited
kinetics characteristic of a slow, tight-binding inhibitor of
7,8-dihydrofolate reduction with bovine liver DHFR (K(I) = 0.109
micromol/L), but of a classic, reversible, competitive inhibitor with
chicken liver DHFR (K(I) = 10.3 micromol/L). Structural modeling showed
that EGCG can bind to human DHFR at the same site and in a similar
orientation to that observed for some structurally characterized DHFR
inhibitor complexes. The responses of lymphoma cells to EGCG and known
antifolates were similar, that is, a dose-dependent inhibition of cell
growth (IC50 = 20 micromol/L for EGCG), G0-G1 phase arrest of the cell
cycle, and induction of apoptosis. Folate depletion increased the
sensitivity of these cell lines to antifolates and EGCG. These effects
were attenuated by growing the cells in a medium containing
hypoxanthine-thymidine, consistent with DHFR being the site of action
for EGCG.

PMID: 15781612

So green tea and mtx both inhibit DHFR. Do we need more folate then, if
taking green tea caps? I'm thinking of you know who right now.

You cruiser! Your taking a bomber load of Green tea, right?

You need it then. But,

It really hasn't made much difference over the years that i'm aware of.
Not
like many many other things i've taken. Even curcumin gives a better
punch for
the buck and that's not much.

http://www.ncbi.nlm.nih.gov/entrez/...t_uids=14529545

This next one has the B12 link to folates,

http://www.ncbi.nlm.nih.gov/entrez/...t_uids=12720045

Anemia, serum vitamin B12, and folic acid in patients with rheumatoid
arthritis, psoriatic arthritis, and systemic lupus erythematosus.

Segal R, Baumoehl Y, Elkayam O, Levartovsky D, Litinsky I, Paran D,
Wigler I, Habot B, Leibovitz A, Sela BA, Caspi D.

Department of Geriatrics, Shmuel-Harofeh Geriatric Medical Center, Baer
Yaakov, Israel. shmuelh@netvision.net.il

OBJECTIVE:Although anemia is frequent in inflammatory rheumatic
diseases, data regarding vitamin B12 status is scarce. The purpose of
this study was to analyze the incidence and nature of B12 and folic
acid (FA) deficiencies in a cohort of rheumatic patients with
rheumatoid arthritis (RA), psoriatic arthritis (PsA), and systemic
lupus erythematosus (SLE). METHODS: Levels of B12, FA, and parameters
of anemia were recovered or examined in 276 outpatients. In those with
recent findings of low serum B12 levels, further studies of serum
homocysteine (Hcy) and urine methylmalonic acid (MMA) levels were
performed. RESULTS: The incidence of anemia was high: 49%, 46%, and
35%, in RA, SLE, and PsA, respectively. Low levels of serum B12 were
also frequent (24%), with almost similar occurrence in the three
disease groups. Deficiency in FA was rare (<5%). Mean levels of both
vitamins did not differ significantly among the three groups. No
correlation between serum B12 levels and anemia was found. In the 15
patients with recently detected low B12 levels, Hcy and MMA were
evaluated before and following B12 therapy. In ten of them, baseline
Hcy levels were high, while MMA was increased in one patient only.
Response to B12 administration, i.e., a decrease in Hcy and/or MMA
levels, was noticed in four patients only, suggesting that only 26% of
the low-serum-B12 patients had true B12 deficiency. CONCLUSIONS: The
incidences of anemia and decreased serum B12 levels were high in these
three groups of rheumatic patients. However, true tissue deficiency
seems to be much rarer.

PMID: 12720045

Yet, I see no magic here or when I take them.

As to all the B vits used in synergy i really only see YELLOW pee.

And the same old other P.

randall