I got a reply back from MTHFRsupport. They say
"several doctors and PhDs have told [them] that excessive methylfolate can back up into folic when the liver cannot clear it out. Unmetabolized folic acid has been known to burn out folate receptors in the brain. If you overdo methylfolate it can also back up."
How much is too much? I don't think there is really any hard data for methylfolate at this time.*** (see below)
For folic acid, however, there is data. In general, the amount that causes unmetabolized folic acid is anything above 1000mcg. There is a wide variability in what can be tolerated for each person, dependent on the DHFR gene.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730961/
This blog post says
"The NMCD webstite cautions, ‘Clinical research shows that taking folic acid daily in doses of 800-1200 mcg for 3-10 years significantly increases the risk of developing cancer and adverse cardiovascular effects compared to placebo."
But other info is showing only 200mcg+ causing problems.
http://mthfr.net/l-methylfolate-not-needed-come-on/2011/09/26/
"Also, according to the NMCD, researchers have recommended that “Doses above 1000 mcg per day should be avoided if possible to prevent precipitation or exacerbation of neuropathy related to vitamin B12 deficiency. However, there is some evidence that doses of 5 mg per day orally for up to 4 months can be used safely if vitamin B12 levels are routinely measured."
Now this makes me think that all these folic acid tests were done independent of B12 supplementation...hmmm....that probably changes the game.
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MTHFRsupport also says there are other variables as to why some people might not absorb methylfolate as well as others:
"NAT2 G590A's have trouble with folate and alcohol metabolism in the liver
COMT's who are niacin deficient and the catalytic activity is 5MTHF and NAD.
DHFR's that have trouble converting folic into folate.
Someone with FOLR's already have compromised folate receptors."
These SNPs can probably be pulled via Sterling's App.
I also found info regarding milk causing cerebral folate antibodies, which would inhibit folate receptors.
http://forums.phoenixrising.me/index.php?threads/folate-receptor-antibodies.22653/
So if you were having trouble metabolizing methylfolate, you would want to avoid milk (dairy). Then if you had COMT, make sure you weren't niacin deficient, and supplement if you were. If you had NAT, avoid alcohol? If you had DHFR and FOLR, I don't think there's anything you could do except be aware that you genetically don't absorb as well as others.
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***However, since methylfolate is better absorbed than folic acid, the amount that can be metabolized should be higher than the folic acid amount.
This blog post on MTHFR.net says that there are studies showing methylfolate absorbs either 2 to 7 times better than folic acid, or around 31-39% better.
http://mthfr.net/l-methylfolate-not-needed-come-on/2011/09/26/
Extrapolating from this data - this amount of
methylfolate would absorb the same as this amount of
folic acid, and if you go any higher (without B12 supplementation?), you may end up with unmetabolized folate.
On a daily basis, for several years:
(
200mcg x 31%) = 62 , so 200 +62mcg =
262mcg
(
200mcg x 39%) = 78, so 200 +78 =
278mcg
800mcg x 31% = 248, 800 + 248 =
1048mcg
800mcg x 39% = 312, 800 + 312 =
1112mcg
1200mcg x 31% = 372, 1200 + 372 =
1572mcg
1200mcg x 39% = 468, 1200 + 468 =
1669mcg
200mcg x 2 =
400mcg
200mcg x 7 =
1400mcg
800mcg x 2 =
1600mcg
1200mcg x 2 =
2400mcg
800mcg x 7 =
5600mcg
1200mcg x 7 =
8400mcg
4 months only:
5000mcg x 31% = 1550, 5000 + 1550 =
6550mcg
5000mcg x 39% = 1950, 5000 + 1950 =
6950mcg
5000mcg x 2 =
10,000mcg
5000mcg x 7 =
35,000mcg
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Ben Lynch says:
"In the meantime, for those wanting to evaluate their unmetabolized folic acid levels and methylfolate levels, I do recommend ordering the Unmetabolized Folic Acid Test by Metametrix...Stop guessing and identify if your methylfolate levels are where they should be."
http://www.seekinghealth.com/unmetabolized-folic-acid-serum.html
I think especially if I was taking high doses of methylfolate, I would be monitoring levels with this test, just to make sure...