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Folic acid and folinic acid can block metafolin inducing deficiency called "ddtox"

Adster

Senior Member
Messages
600
Location
Australia
Thanks Adster -- I'm glad it works for you, but antihistamines increase my tension big time -- I think because they tend to constrict blood vessels and reduce circulation (???). They make give my legs almost instant "RLS". :(

I used to be able to take them 20 or so years ago, but just cannot tolerate 'em at all.

But I appreciate your reply.

Ugghh sounds bad. Hang in there hey. Interestingly I can't take benzo type sleeping drugs like temazepam as I get sleep apnea. Which is scary enough when you aren't doped out lol.
 

JPV

ɹǝqɯǝɯ ɹoıuǝs
Messages
858
Some members of this site have claimed to have gotten relief from CFS symptoms by using antacids...

Tagamet (cimetidine) for CFIDS (worked for me)
http://books.google.com/books?id=VtHlTVfToiQC&pg=PA196&lpg=PA196&dq=Tagamet+and+Chronic+Fatigue+Syndrome&source=bl&ots=G9BEFYa_7z&sig=OUvOZ-6ZCJS3-ZkcTAt7YZwPH7c&hl=en&ei=k59AS7HjE86PlAfY46WnDg&sa=X&oi=book_result&ct=result&resnum=3&ved=0CBAQ6AEwAg#v=onepage&q=Tagamet%20and%20Chronic%20Fatigue%20Syndrome&f=false

http://www.lef.org/magazine/mag2001/mar2001_report_tagamet_1.html

I've been taking it for about a month, and I am 90% recovered after a very long, painful relapse. I'm not cured by any means, but I'm functional and able to return to work. Just be careful because it interacts with many other medications. If you're going to try it, you MUST check drug interactions first. Especially Wellbutrin. (I learned that the hard way - nausea, vomiting, vertigo, and racing heart.) It can interfere with the absorption of many drugs, either increasing or decreasing their effectiveness. So please just be careful if you decide to try it.

Good luck!
So, on a hunch I went searching for another possible explanation as to why antacids might provide some people with relief. Not sure if it's really relevant but it might be worth looking into...

Nutrient Depletions Caused By Antacids

Folic acid Use of antacids (containing aluminum and magnesium hydroxide) may reduce folic acid absorption. Sulfasalazine can lead to a folate deficiency for which supplementation may be necessary. Folic acid absorption from the small intestine is optimal at pH 5.5 to 6, therefore the increased pH associated with the use of H2 blockers (such as cimetidine (Tagamet), famotidine (Pepcid), nizatidine (Axid), and ranitidine (Zantac)) can reduce folic acid absorption.

I was also thinking that maybe gluten is not so much a problem, for some people, as is the folic acid that is added to wheat products.
 

rwac

Senior Member
Messages
172
I was also thinking that maybe gluten is not so much a problem, for some people, as is the folic acid that is added to wheat products.

Yikes. Several people I know specifically can't tolerate wheat in the US, but are fine eating it elsewhere.
Is supplementing flour with folic acid unique to the US ?

It's either the folic acid, or the US uses an strain of dwarf wheat which has especially bad gluten proteins.
 

JPV

ɹǝqɯǝɯ ɹoıuǝs
Messages
858
Yikes. Several people I know specifically can't tolerate wheat in the US, but are fine eating it elsewhere.
Is supplementing flour with folic acid unique to the US ?

It's either the folic acid, or the US uses an strain of dwarf wheat which has especially bad gluten proteins.
Numerous countries do it but I don't think that all of them do. Plus they have different dosages that they employ.
 

leaves

Senior Member
Messages
1,193
Ehh I cant tolerate gluten anywhere.. Not in minute amounts, nothing to do with folate for me.
 

drex13

Senior Member
Messages
186
Location
Columbus, Ohio
Yikes. Several people I know specifically can't tolerate wheat in the US, but are fine eating it elsewhere.
Is supplementing flour with folic acid unique to the US ?

It's either the folic acid, or the US uses an strain of dwarf wheat which has especially bad gluten proteins.

I think the politically correct term is "little person". Or maybe "little wheat".
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
A couple of things more on folic acid. I have talked to some company prodeuctr development people. The folic acid in b-compelx is being taken care of, I don't know how fast, but pretty soon. They were aware of some of the problems and we will have a solution. The question is when.

Now as far as timing goes. Since a week ago I have removed the Metafolin from the times I take folic acid figuriong the folic acid was blocking it. Appraently that works both ways as I ended up with fast onset of folate deficiency despite taking 8800mcg of Metafolin at other times. So it looks like this now. At the absorbtion level, folic acid, folinic acid and mrhtylfolate all compete, so reducing Metafolin increases folic acid absorption. Then the folic acid competes for transport and the symptoms got far worse very rapidly. So yesterday I switched back to Metafolin with the folic acid and at other times and things are improving today. I have been through this so often now I recognize first or second day changes in both directions. Right now I am working out an optimal folic acid blocking timing. For now, my experience suggests taking Metafolin with anything with folic acid in it to minimize absorption and then at several other times per day. I know that taking 2400mcg Metafolin with 400 mcg of folic acid allows the Metafolin to predominate. Taking the folic acid without the metafolin allows it to block the Metafolin 24 hrs/day. Folinic acid was even worse. As I have said previously, timing is important for best effects. I hope this is all different pretty soon. At least we do have a way to make it effective despite folic acid but not with folinic acid.
 

Rockt

Senior Member
Messages
292
Thanks for this Fred.

Question: where does that leave Jarrow B-Right? Since it has folic acid, should it be discontinued or taken in conjunction with Metafolin? Just got a full bottle in the mail yesterday, so I'm hoping I can use it.
 

L'engle

moogle
Messages
3,187
Location
Canada
Ok, so that means if I take the dibencozide with 200mcg of folic acid in it, theoretically I could block the folic acid with 1600 mcg of metafolin taken at that time. And it is good to take it at other times I gather. Good to know you are finding that the metafolin can block the folic acid as well as the other way around.

Would be great I guess if country life made a formulation without folic acid.
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Ok, so that means if I take the dibencozide with 200mcg of folic acid in it, theoretically I could block the folic acid with 1600 mcg of metafolin taken at that time. And it is good to take it at other times I gather. Good to know you are finding that the metafolin can block the folic acid as well as the other way around.

Would be great I guess if country life made a formulation without folic acid.

Hi L'engle,

There are a fair number of folks who are going to try Source Naturals Dibencozide. Here is hoping that it absobs well and is effective. I will A-B it for alternating months and see.
 

toddm1960

Senior Member
Messages
155
Location
Rochester, New York
Rich what is the difference in folic acid, folinic acid and leucovorin? As part of my mitochondrial testing with Dr Shoffner he found very low levels of 5-methyltetrahydrofolate in my CSF, and I take 25mg of leucovorin three times a day. Could this take the place of metafolin? Should I stop the leucovorin while I try the methylation?
 

richvank

Senior Member
Messages
2,732
Rich what is the difference in folic acid, folinic acid and leucovorin? As part of my mitochondrial testing with Dr Shoffner he found very low levels of 5-methyltetrahydrofolate in my CSF, and I take 25mg of leucovorin three times a day. Could this take the place of metafolin? Should I stop the leucovorin while I try the methylation?

Hi, toddm1960.

Folic acid is the oxidized form of folate. It is not found in natural food sources, but in the U.S. and some other countries it is added by law to food grains in order to lower the incidence of neural tube birth defects, such as spina bifida. Folic acid is also the most common commercially sold form of folate. It has a long shelf life, because it is already oxidized. In order for the body to use it, it must be chemically reduced to tetrahydrofolate. This is done mostly in the liver, using the enzyme dihydrofolate reductase (DHFR) to catalyze two sequential reactions.
There is a factor of five range in the rate of the first reaction among different people owing to genetic differences, and some people are not able to use folic acid very well for this reason. There is some evidence that folic acid, if it builds up in the blood stream, can inhibit the natural killer cells, and thus may influence the risk of cancer, but this issue is still unresolved.

Folinic acid and leucovorin are the same substance, 5-formyl tetrahydrofolate. Folinic acid occurs naturally in the body and in natural food sources. It is one of the chemically reduced forms of folate. The body does not use it directly as a coenzyme, but converts it to other folate coenzyme forms. The conversion of folinic acid to 5-methyl tetrahydrofolate requires three sequential reactions. If there are downregulating genetic polymorphisms in one or more of the enzymes that catalyze these reactions, it may be difficult to make this conversion.

I cannot advise you about whether it would be better for you to take Metafolin than leucovorin, but you can consider the biochemistry described above together with your physician, and make your own decision.

Best regards,

Rich
 

rwac

Senior Member
Messages
172
Folinic acid is racemic.

At least we do have a way to make it effective despite folic acid but not with folinic acid.

Hi Freddd,

I don't know if you already know this but Folinic Acid is a racemic product, and the inactive isomer tends to block the active isomer. This might be the reason for your bad reactions to it. The same goes for Leucovorin, but Levoleucovorin is only the active isomer.

http://www.ncbi.nlm.nih.gov/pubmed/7483142
 

Freddd

Senior Member
Messages
5,184
Location
Salt Lake City
Rich what is the difference in folic acid, folinic acid and leucovorin? As part of my mitochondrial testing with Dr Shoffner he found very low levels of 5-methyltetrahydrofolate in my CSF, and I take 25mg of leucovorin three times a day. Could this take the place of metafolin? Should I stop the leucovorin while I try the methylation?

Hi Toddm,

Taking leucovorin could be blocking methylfolate if you are like some of us here and cause or maintain deficiency symptoms and block methylation. 25mg 3 times a day would completely shut down my Metafolin and put me into severe deficiency. That is why it is PARADOXICAL folate deficiency. It is your consideration what to do. Fortunately the folinic acid will leave your system withn a day or so and then you could try a couple of weeks on Metafolin. The difference would be very obvious within a few days if the folinic acid is having a paradoxical effect on you. Good luck.
 

rwac

Senior Member
Messages
172
Also, D-Folinic Acid Accumulates in plasma.

[l-folinic acid versus racemic folinic acid in the treatment of leukemia in children with high dose of methotrexate].
Etienne MC, Thyss A, Bertrand Y, Rubie H, Milano G.

Centre Antoine-Lacassagne, Nice, France.


Abstract
Until now, folinic acid (FA) has been available the racemic mixture d1 FA, whose biological activity is supported by natural 1 FA. The purpose of this trial was to compare, on a pharmacokinetic, biological, and clinical basis, the racemic mixture dl FA with the pure 1 FA in the rescue of high-dose methotrexate (MTX) therapy. Eighteen children with acute lymphocytic leukemia (ALL) were entered in this trial planned with a cross-over design. Four cycles of MTX (5 g/m2, 24h CVI) were administered to each patient, with a 2-week interval between cycles. The rescue was achieved orally every 6h, starting 12h after the end of the MTX infusion, at a dose of 12 mg/m2 for dl FA and 6 mg/m2 for pure 1 FA. dl FA and 1 FA rescues were alternated from one cycle to the next. d FA, 1 FA, and the active metabolite 5-methyltetrahydrofolate (5-MTHF) were measured in plasma using a stereospecific HPLC assay. After administration of dl FA, the accumulation of d FA in plasma was confirmed: mean residual concentrations were 420 and 652 nM after 2 and 6 intakes respectively. Total active folate concentrations (1 FA + 5-MTHF) were similar between the two types of rescue: 92 and 100 nM respectively for dl FA rescue and 1 FA rescue after two intakes, 186 and 184 nM respectively for dl FA rescue and 1 FA rescue after six intakes. Intra-individual statistical analysis of total active folates (1 FA + 5-MTHF) performed on 17 patients did not show any significant difference between dl FA rescue and 1 FA rescue. For both types of rescue, MTX terminal half-lives were identical (average value 13.9 h). Considering each type of toxicity (hematologic, hepatic, renal and digestive) there was no significant difference in the proportion of toxic cycles following l FA rescue or dl FA rescue. In conclusion, the administration of the pure l FA, as compared with the administration of the racemic mixture, results in comparable blood profiles of active folates and MTX, and leads to equivalent treatment tolerance.

This review indicates a subtle difference between the active isomer and the racemic form. It doesn't rise to statistical significance though.

Is levoleucovorin an alternative to racemic leucovorin? A literature review.

Kovoor PA, Karim SM, Marshall JL.

Georgetown University, Washington, DC, USA.
Abstract

PURPOSE: Our purpose is to perform a comprehensive literature review of the use of levoleucovorin in gastrointestinal malignancies and to assess whether levoleucovorin is a reasonable alternative to racemic leucovorin.

DESIGN: This is an extensive literature review of levoleucovorin use in patients with gastrointestinal tract malignancies. Our review revealed 125 citations with abstracts in the English language, including 16 randomized, controlled trials; 40 case studies; and 69 nonrandomized, controlled trials that included 6 pharmacokinetic (PK)/pharmacodynamic studies with 1 population PK study.

RESULTS: Upon our review, there were 2 randomized controlled trials that directly compared racemic leucovorin with levoleucovorin. Goldberg et al noted that there was no statistically significant difference between time to progression (P = .78) and time to death (P = .57). Furthermore, Scheithauer et al again noted no significant difference in terms of response rates (25% vs. 32%; P = .25), median survival time (15 months vs. 14.5 months; P = .28), overall survival at 1 year (58.3% vs. 60.6%; P = .72), and probability of survival at 2 years (15.3% vs. 23%; P = .16). In addition, multiple other studies, including randomized, controlled; nonrandomized, controlled; and case studies, demonstrate similar efficacy and tolerability between the use of racemic leucovorin or levoleucovorin as a modulator of 5-FU.

CONCLUSION: In many studies of patients with gastrointestinal malignancies, levoleucovorin has been used interchangeably and solely for racemic leucovorin for 5-FU modulation. Our literature review demonstrates that levoleucovorin has similar efficacy and tolerability when compared with racemic leucovorin, whether used in combination with other chemotherapeutic agents or alone.
 

toddm1960

Senior Member
Messages
155
Location
Rochester, New York
Thank you for your help, it sounds like the best path is to follow the methylation formula as is and take a break from the leucovorin. Do you know of any others with mitochondrial dysfunction that have been helped trying this?
 

SJB944

Senior Member
Messages
178
Given that B-right has Folic acid in it, is there any consensus on a viable alternative? I've seen a few mentioned here and there on the forum, has any one tried and tested a good one?

Kind regards
SJB944
 

JPV

ɹǝqɯǝɯ ɹoıuǝs
Messages
858
Hi Jpv,

I think that an updated poll needs to be done including methylfolate. This dates way back.

Your plan has always included methylfolate, hasn't it? Or do you mean your new approach to taking it?