20 replies to this topic

[garcia]

Hi all,
does anyone know what the effects of folinic acid supplementation are on Dopamine and Stomach acid/hcl? I know folinic acid raises serotonin levels, but does it also raise dopamine levels? Also when I take folinic acid I sometimes get a very acid stomach. Does anyone know what the mechanism might be behind this?

Many thanks.
garcia.

[Lufega]

some kind of increased cholinergic activity? I get the same effect from centrophenoxine and citicoline.

Dietary and genetic compromise in folate availability reduces acetylcholine, cognitive performance and increases aggression: critical role of S-adenosyl methionine.

Chan A, Tchantchou F, Graves V, Rozen R, Shea TB.

Center for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, University of Massachusetts, Lowell, MA 01854, USA.

Folate deficiency has been associated with age-related neurodegeneration. One direct consequence of folate deficiency is a decline in the major methyl donor, S-adenosyl methionine (SAM). We demonstrate herein that pro-oxidant stress and dietary folate deficiency decreased levels of acetylcholine and impaired cognitive performance to various degrees in normal adult mice (9-12 months of age, adult mice heterozygously lacking 5',10'-methylene tetrahydrofolate reductase, homozygously lacking apolipoprotein E, or expressing human ApoE2, E3 or E4, and aged (2-2.5 year old) normal mice. Dietary supplementation with SAM in the absence of folate restored acetylcholine levels and cognitive performance to respective levels observed in the presence of folate. Increased aggressive behavior was observed among some but not all genotypes when maintained on the deficient diet, and was eliminated in all cases supplementation with SAM. Folate deficiency decreased levels of choline and N-methyl nicotinamide, while dietary supplementation with SAM increased methylation of nicotinamide to generate N-methyl nicotinamide and restored choline levels within brain tissue. Since N-methyl nicotinamide inhibits choline transport out of the central nervous system, and choline is utilized as an alternative methyl donor, these latter findings suggest that SAM may maintain acetylcholine levels in part by maintaining availability of choline. These findings suggest that dietary supplementation with SAM represents a useful therapeutic approach for age-related neurodegeneration which may augment pharmacological approaches to maintain acetylcholine levels, in particular during dietary or genetic compromise in folate usage.

This presentation also states folic acid is a cofactor for ACh production...dopamine too! See page 8

http://www.science.m...ocuments/yu.pdf

Edited by Lufega, 04 November 2009 - 11:55 PM.

[garcia]

Thanks a lot for that Lufega, it was very useful! Good to know that it increases dopamine and acetylcholine too.

[wolfeye]

folates appear to influence the rate of synthesis of tetrahydrobiopterin (BH4)

http://www.medscape....431514_sidebar1

Tetrahydrobiopterin is a cofactor of the three aromatic amino acid hydroxylase enzymes, used in the biosynthesis of the neurotransmitters serotonin, melatonin, dopamine, noradrenaline, adrenaline and nitric oxide.

http://en.wikipedia....ahydrobiopterin

Edited by wolfeye, 06 November 2009 - 05:22 PM.

[Lufega]

Thanks for that wolf. I was trying to connect folic acid with BH4 and couldn't find anything. There's a type of dysautonomia that is caused by folic acid def. It's about the only thing I haven't tried. I also have a long standing anemia.

"Among the myriad transmethylation reactions involving the 1-carbon cycle, which are most relevant to the relationship between folate and depressive disorders remains a matter of speculation. Both folates and SAMe appear to influence the rate of synthesis of tetrahydrobiopterin (BH4), the cofactor in the hydroxylation of phenylalanine and tryptophan.[11-13] Since this is the rate-limiting step in the biosynthesis of dopamine, norepinephrine, and serotonin--neurotransmitter systems that are thought to be involved in the pathophysiology and treatment of depressive disorders--alterations in the rate of synthesis of this important cofactor may be relevant to depression.[14"

Edited by Lufega, 06 November 2009 - 07:40 PM.

[Lufega]

Results are back. Folic acid levels are 9.81. Range is 3 - 17 ng/ml. However, I wonder if supplementing will produce a therapeutic effect?

[wolfeye]

Psychs use Deplin (7.5 mg) to potentiate ADs. An insane dose in my opinion. 400-800 mcg would be more adequate.

[VespeneGas]

Pardon my ignorance, as I'm new to the whole methylation scene, but does folinic acid bypass Methylenetetrahydrofolate reductase, getting converted into methylfolate through some other mechanism? If so, why is methylfolate preferred for those T-homozygous for this gene? How are their metabolic effects different? If not, why is it preferred over folic acid for anyone not taking dihydrofolate reductase inhibitors or methotrexate?

[Stephen Fleming]

Hi Guys,
This is Stephen, Folinic acid, also known as 5-formyl tetrahydrofolate, is an active form of a group of vitamins known as folates. In contrast to folic acid, a synthetic form of folate, folinic acid is one of the forms of folate found naturally in foods. Folate deficiency is believed to be the most common vitamin deficiency in the world due to food processing, food selection, and intestinal disorders. In the body folinic acid may be converted into any of the other active forms of folate.

[stephen_b]

Hi Guys,
This is Stephen, Folinic acid, also known as 5-formyl tetrahydrofolate, is an active form of a group of vitamins known as folates. In contrast to folic acid, a synthetic form of folate, folinic acid is one of the forms of folate found naturally in foods. Folate deficiency is believed to be the most common vitamin deficiency in the world due to food processing, food selection, and intestinal disorders. In the body folinic acid may be converted into any of the other active forms of folate.

Stephen, you are quoting advertising copy verbatim from a folinic acid product. You might want to try raising the bar a bit on your contributions to this forum.

[VespeneGas]

Bumping this for an answer to my question

[stephen_b]

Bumping this for an answer to my question

Krillin thinks so.

[VespeneGas]

Bumping this for an answer to my question

Krillin thinks so.

Thanks!

[wolfeye]

I've seen many claims on the internet that folates will increase histamine.
I just can't find any logical explanation to these claims.
What is the biological connection between folate and histamine?

[neogenic]

Folinic acid, the formyl-folate, is 1 off from the 5-mthf active form. The reason so many have folate enzyme issues in the population is there is 5 steps to convert folic acid to 5-mthf. The folinic acid/formyl version is a vast improvement over standard supplementation forms, but falls short of 5-mthf the most superior form. The problem is that Big Pharma came and snatched it up. Metafolin is now a patented ingredient owned by Merck.

LEF does have it. It is difficult to acquire the licence for. Thorne and Solgar have versions as well. They are very picky about which supplement companies can have it and won't let you dose at or above 1mg.

Bottom line is folic acid isn't effective for a massive number of the population, I think its 1/3 has enzyme deficiencies.
Folinic acid is a one off, but a great improvement over folic acid.
Metafolin is the most superior, but harder to find and expensive.

[stephen_b]

Nice bottom line summary. I wonder though if 1 mg methylfolate isn't sufficient for most people.

[VespeneGas]

Nice bottom line summary. I wonder though if 1 mg methylfolate isn't sufficient for most people.

Why supplement with more than the RDA in the absence of disease, given that methylfolate is already in its active form, and supplemental folate is absorbed significantly better than folate from food? Are there some benefits kismet's not telling me about? Potentially increasing cancer risk for speculative benefits from lowering elevated homocysteine? "Most people" probably do not need supplemental folate in any form (IIRC only roughly 10% of the population has the relevant polymorphism).

[stephen_b]

Why supplement with more than the RDA in the absence of disease, given that methylfolate is already in its active form, and supplemental folate is absorbed significantly better than folate from food? Are there some benefits kismet's not telling me about? Potentially increasing cancer risk for speculative benefits from lowering elevated homocysteine? "Most people" probably do not need supplemental folate in any form (IIRC only roughly 10% of the population has the relevant polymorphism).

The science isn't clear that 1) the unmetabolized folic acid isn't the cause of the increased cancer risk and 2) whether there are benefits to an increased intake of l-methylfolate in excess of the RDA. The prudent thing to do is probably to err on the side of caution.

Another issue is that looking at folate in isolation from B6 and B12 might skew one's conclusions towards folate being dangerous.

Edited by stephen_b, 06 December 2009 - 02:39 AM.

[krillin]

Bumping this for an answer to my question

Krillin thinks so.

That is a misreading of what I wrote. VespeneGas was asking about MTHFR, not DHFR. Only 5-MTHF bypasses the former, while both it and folinic acid bypass the latter. Bypassing DHFR prevents unmetabolized folic acid from getting into circulation, while bypassing MTHFR is pretty pointless, since folates go through the MTHFR enzyme many many times during their long biological lifetimes. The MTHFR polymorphism causes the MTHFR cofactor vitamin B2 to not stick very well, and is treatable with small doses of B2.

The real reason that 5-MTHF is preferable over folinic acid is that the Metafolin brand is chirally pure, while the folinic acid on the market is racemic. (LEF's 5-MTHF, however, appears to be racemic based on their product label.)

Here is the best methylation diagram I've encountered.

http://www.lipidworl...5/1/1/figure/F1

I think a folate target of 18-23 nM looks reasonable (PMID: 9758112).

Although we failed to find a significant relationship between serum folate and all-cause mortality and circulatory disease, plots of the log relative hazard and serum folate concentration suggested a J-shaped relationship between the risk of disease and serum folate concentration with the lowest risk occurring around serum folate concentrations of 18-23 nmol/l.

That's 7.9-10.2 ng/ml, which is about the 80th-90th percentile. Which corresponds to 400-475 mcg/day. The RDA isn't so bad after all. My apologies to Michael for doubting him on this.

[ramon25]

Why supplement with more than the RDA in the absence of disease, given that methylfolate is already in its active form, and supplemental folate is absorbed significantly better than folate from food? Are there some benefits kismet's not telling me about? Potentially increasing cancer risk for speculative benefits from lowering elevated homocysteine? "Most people" probably do not need supplemental folate in any form (IIRC only roughly 10% of the population has the relevant polymorphism).

The science isn't clear that 1) the unmetabolized folic acid isn't the cause of the increased cancer risk and 2) whether there are benefits to an increased intake of l-methylfolate in excess of the RDA. The prudent thing to do is probably to err on the side of caution.

Another issue is that looking at folate in isolation from B6 and B12 might skew one's conclusions towards folate being dangerous.

So then logically to err on the side of caution means to supplement the rda and also get the other b's in too because too take to much might be baad and to not have enough might alos be bad. So supplement but be moderate and balanced. Nothing new here.....

[John Barleycorn]

Here is the best methylation diagram I've encountered.

http://www.lipidworl...5/1/1/figure/F1

Although less detailed, I've found Fig 2 in this paper to be handy as well: http://www.thorne.co...t/13/3/216.pdf.

Note that betaine should arguably be replaced with the less ambiguous term TMG.