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High Need For Folate?

T

Tigger

Messages
94
Hi,

I have had unbelievalbe success with @Freddd's protocol versus more than a year and a half of taking it slow on others protocols. I am currently at 15 mg methylfolate (via methylpro) x2/day and Jarrow methylcobalamin 1.25 mg x2/day with quite a bit of success. I also support with ab12 and potassium gluconate. However, I notice that within 3-5 hours of taking the dose, I lose all the benefits. I am slower, thinking less clearly, less muscle strength, etc. I know the half-life of methylfolate is 6 hours but I am obviously taking an extremely large dose. Anyone have any idea why I have such a high need for folate? I take all supporting co-factors.
 
E

Eastman

Senior Member
Messages
526
Didn't you say you suspect you have heavy metal toxicity in another thread? As caledonia mentioned there, some metals inhibit methylation at methionine synthase (MTR).

Also, I found this paper which said that the methionine synthase pathway is potently inhibited by ethanol, lead, mercury, aluminum and thimerosal.
 
T

Tigger

Messages
94
Thanks for the response. I do and am currently taking ALA per Cutler's protocol. I'm hoping that within 6 months to a year the ALA will have helped enough that I won't need such a high dose of folate. I don't have a problem with taking so much but am just curious as to why the need is so great.
 
A

alicec

Senior Member
Messages
1,572
Location
Australia
Tigger said:
Anyone have any idea why I have such a high need for folate? I take all supporting co-factors.
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You may not be recycling it efficiently. This in turn could be due to failure to efficiently convert riboflavin to the actIve form (FAD) which is the cofactor for the MTHFR enzyme. This enzyme remethylates folate after it has been used in the methionine synthase reaction.

There is a thread discussing some ideas about what is necessary to make FAD. Some people have found that this has enabled them to reduce folate need considerably.

Others, including myself, have found this somewhat helpful but not the whole story. There could be other places in the folate cycle where inefficiencies occur.
 
T

Tigger

Messages
94
Thanks for that link.

Would taking R5P as opposed to regular B2 help solve this problem?

How did you pursue the B2 issue?

The only hesitation I have is that B2 may actually further the need for folate (at least according to Freddd).
 
A

alicec

Senior Member
Messages
1,572
Location
Australia
Tigger said:
Would taking R5P as opposed to regular B2 help solve this problem?
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That is controversial. Here is a post I made about it and there is more discussion in that thread. Theoretically, at least according to the most studied mechanisms of uptake and processing of B2 and B6, there is no point in taking R5P or P5P. Furthermore, sublingual uptake may not happen the way we think it does (actually it just provides a slow trickle into the gut).

BUT, a number of people, myself included, have found that there is definitely a difference in response to sublingual R5P and P5P, compared with riboflavin and pyridoxine. There have been a couple of small studies that suggest alternative uptake processes occur but really it is a bit of a mystery.

Tigger said:
How did you pursue the B2 issue?
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I need to update on the report that @Eastman has kindly linked. I think I have partially updated somewhere but have now forgotten what I put where! Plus I am in the middle of some experimenting so was waiting to make a more complete update.

Anyhow things have moved on a lot since that post. Essentially that B2 stuff has been part of a much wider search to sustain the benefits of B12/folate. This has been a very beneficial intervention for me but various things have gone wrong, including becoming more sensitive to B12 than I used to be.

I believe depletion of several minerals and some B vitamins has been behind this (posts here and here) and now that I have been able to tolerate and apparently need huge doses of methylB12, my folate needs have increased considerably again.

So, as I said above, I don't think Greg's ideas cover the whole story but are certainly helpful.

Tigger said:
The only hesitation I have is that B2 may actually further the need for folate (at least according to Freddd).
Click to expand...

I and others on the thread discussing B2 found the opposite.

It is worth experimenting with, there seems to be a variety of responses.
 
T

Tigger

Messages
94
Thank you so much for your responses. I don't mind taking the high-dose folate but it is undoubtedly more expensive and seems like overkill. I think the best thing for me at this point is to carefully experiment and document an addition of B2 while keeping other variables constant. Thanks again.
 
A

alicec

Senior Member
Messages
1,572
Location
Australia
Thought I should add that some people reported that R5P was very helpful in the beginning (ie it did something that riboflavin didn't) but later they could revert to plain riboflavin.

I am pretty sure this is happening with me, though haven't finished the experiment yet.

I don't understand the mechanism at all - actually it doesn't really make sense but it does seem to happen.
 
Hip

Hip

Senior Member
Messages
17,857
Tigger said:
Anyone have any idea why I have such a high need for folate?
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When taking super high dose vitamins, it possible that the benefits you obtain are nothing to do with satisfying the nutritional requirements of that vitamin.

People often assume that when benefits are observed from very high doses of vitamins or minerals, that implies you are deficient in those nutrients.

However, this many not be the case, because high dose vitamins or minerals can have effects that are beyond the normal nutritional roles of that vitamin or mineral.

So the benefits you gain from super high dose methylfolate may be nothing to do with your nutritional requirements for that vitamin.
 
stridor

stridor

Senior Member
Messages
873
Location
Powassan, Ontario
First things, first. You need to make sure that you are absorbing it in the first place. I gave up trying to swallow mfolate when 9 capsules did nothing for me. Too expensive to follow that through.

I started to put it in the buccal pouch and everything improved. A percentage of people with high folate intake will not be getting it on-board.
 
T

Tigger

Messages
94
Thank everyone.

@stridor What brand are you taking and how does that work? I'm currently taking MethylPro 15 mg capsules. I notice a massive difference and believe I have decent gut health but I would obviously go for a more effective route if possible.
 
stridor

stridor

Senior Member
Messages
873
Location
Powassan, Ontario
@Tigger
I might notice a difference if I were to take as much as you do orally as well. I found it to be expensive. The question is whether a person is actually using that much or whether it is simply the amount that they need to take to have enough absorbed.

The same goes for some of us with mB12. I still take 2 needles a day. I think that is just what it takes to have enough get into the cells. I do not believe that my body goes through 2 years worth of B12 every day.

Currently, I am using Jarrow but I have used 3 and maybe 4 other brands and they all worked the same. When I was the sickest....and this is before the infections were found....I would take 3+ capsules a day this way. Now I take around 1 x 1000 mcg.

When I was sick the degree of brain-fog told me that I needed a dose. I also have a hard time to get iron and B2 on board and there may be others. My gut is an on-going project.
 
T

Tigger

Messages
94
Hmmm. Be tried lithium orotate before but not in conjunction with folate/mb12. I wonder if that would help with absorption.
 
Gondwanaland

Gondwanaland

Senior Member
Messages
5,094
Gondwanaland

Gondwanaland

Senior Member
Messages
5,094
J Biol Chem. 1984 Jan 10;259(1):12-5.
Inhibition of mammalian xanthine oxidase by folate compounds and amethopterin.
Lewis AS, Murphy L, McCalla C, Fleary M, Purcell S.
Abstract
We have examined the effects of folate compounds and the folate analog amethopterin (methotrexate) as inhibitors of mammalian xanthine oxidase and have found that they offer potent inhibition of the enzyme. We have compared the inhibitory potency of folic acid and its coenzyme derivative tetrahydrofolic acid to that of allopurinol, a known inhibitor of xanthine oxidase, and have demonstrated that folic acid and tetrahydrofolic acid are severalfold more potent than allopurinol as inhibitors of xanthine oxidase. Comparative inhibition constants calculated were 5.0 X 10(-7) M for folic acid. 1.25 X 10(-6) M for tetrahydrofolic acid, and 4.88 X 10(-6) M for allopurinol. Incubation of xanthine oxidase with folic acid at a concentration of 10(-6) M abolished 94% of the enzymic activity within 1 min of incubation with the enzyme. At the same concentration, allopurinol was almost ineffective as an inhibitor of xanthine oxidase. The substrate xanthine protected the enzyme against total inhibition by folic acid. Reversibility of the enzymic inhibition by folic acid was demonstrated. Folic acid-inactivated enzyme was totally regenerated either by filtration through Sephadex G-200 or by precipitation with ammonium sulfate. 2-Amino-4-hydroxypteridine was a poor substrate for the enzyme but a potent inhibitor for the oxidation of xanthine by the enzyme. The inhibition constant calculated was 1.50 X 10(-6) M. In the presence of an excess of xanthine oxidase, neither folic acid nor tetrahydrofolic acid and allopurinol exhibited any change in intensity of their absorbance or in the wavelength of their maximal absorbance that might have been suggestive of substrate utility. The folate analog amethopterin was also determined a potent inhibitor of mammalian xanthine oxidase. The inhibition constant calculated was 3.0 X 10(-5) M.
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I bolded above what I think might represent the sulfur intolerance some people report.


http://www.chiro.org/nutrition/FULL/Ease_Gout_Pain.shtml
High doses of niacin, greater than 50 mg daily, are not recommended for people with gout because niacin competes with uric acid for bodily excretion. Vitamin C in doses greater than 3,000 mg is also contraindicated for gout sufferers because it may increase uric acid in some people. (16)
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A

alicec

Senior Member
Messages
1,572
Location
Australia
Gondwanaland said:
I bolded above what I think might represent the sulfur intolerance some people report.
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Those are just techniques to separate the large enzyme from the small folate molecule. In other words they are showing that folate doesn't bind irreversibly to the enzyme so activity can be restored simply by removing the folate.

The first technique is a sieving mechanism that separates substances based on size, in the second, large amounts of ammonium sulfate cause proteins to come out of solution.

I don't think this is relevant to what happens in vivo.

Great article - I didn't realise folate inhibited xanthine oxidase.
 
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