No, I'm back up to about 3.2 mg folate right now (2 800mcg tabs, twice a day. Sometimes I'll take one more at dinner time.) I've also doubled my mb12 shots to 1 mg daily. Then I also take 6 or so 1mg tabs of mb12 on the assumption that I'm absorbing about 1.5 mg from those (I figure on a 25 percent absorption rate). I also take 8.6mg adb12 daily (which I hope translates to 2 or so mg absorbed).
I'm shooting for a 1 to 1 ratio, mostly because I have no hope of making the 2-1 mb12 to mfolate ratio that Freddd says is best for him. He has access to 10 mg injections that help him get high absorption of mb12. He might also need wildly different amounts of MB12 and mfolate than the rest of us do. He certain was far sicker that I was and for far longer.
My best guess for why I had trouble early on is that some of my snps were messing with my neurotransmitter levels (MAO A and COMT) and methylation startup was increasing that instability. I think starting low and going slow is excellent advice for those of us with those snps, even if we don't feel particularly sensitive to supplements, which I did not think I was when I started.
I was able to raise my levels after a couple months and I'm in a pretty nice upward climb right now, with of course the occasional enormous speed bump because life would be boring if things went well all the time.
I've been as low as 2.5 or 3 activity level this year and right now I'm somewhere between 5 and 6.
I keep meaning to post a thread on this but haven't had time. I have gotten some really interesting feedback from the researcher behind the b12oils.com site. He's a phd who's been researching b12 for 25 years, he says, and this is the analysis he gave of my snps. Since at least one other person on this thread (@
musicchick581 ) has similar snps, I'll paste it in. I find it useful to read this sort of thing even if the genetics are a bit different than mine.
I have not yet trialed the folinic acid he recommends, but I plan to, finances permitting. I am starting on his MB12 transdermal oil and will report back on it's efficacy, as best I can determine it, in a couple weeks.
Looking at how people go with the profiles, I think that the major problems/concerns are really the +/+ mutations. Generally if you have +/- it means that one copy of the protein is working properly. 50% of the population will have +/- so one has to assume that one does reasonably well on it.
Mutations in any of the cycles are cumulative, so that if you have say 2 genes with mutations in the folate cycle, the cycle will run very slowly. It is like a series of large pipes, with one very small pipe in the series. The flow of water depends upon the smallest pipe. Thus if you have +/+ this restricts you flow dramatically. Now the other thing is that all the reactions "back up" behind the restriction.
In the data that I have sent you back you will see a column that has the co-factors (the enzyme helpers) that are required for the enzyme to work properly. With nearly all the mutations, the mutations mean that the enzyme can lose hold of the co-factor if the concentration drops. Thus, if an enzyme needs FAD (from vitamin B2) and there is a mutation in the enzyme, it is critical that you keep the levels of the vitamins very high. You will see that basically you need SAM, FAD and pyridoxal phosphate as the main co-factors.
Going through your mutations (+/+) you can see major problems in your folate cycle with Methylenetetrahydrofolate dehydrogenase, 5,10 methylenetetrahydrofolate synthase, and serine hydroxymethyltransferase. FYI you are the only person that I have seen with this series of mutations as +/+. Your folate cycle will run very slowly. You will also have trouble with utilizing folate (folic acid) as once you have made THF, SHMT is the enzyme for taking it into the folate cycle. I would think that for your folate supplementation you will need to incorporate folinic acid. Your MTHFR alleles means that you will need to also have 5MTHF to run your methylation cycle (obviously you know this. 5MTHF is the normal dietary folate).
Looking at the generation of SAM, which can come via Betaine, 5MTHF/MeCbl/MTR, or methionine, your BHMT +/+ means that supplementing with betaine is probably not going to be great. Now it appears that we evolved to get methyl groups from betaine and up to 50% of SAM is normally generated from betaine.
You have MTRR +/+, which means that your usage of methylB12 is very high, as you can't convert oxidized Co(II)B12 back to Co(III)B12, so you will be continually having to supplement in with more MeCbl. The other problem is that you wil basically not be able to supplement with CN-B12, because you use MTRR and decyanase to kick the CN group out of CN-B12. Studies also suggest that hydroxyB12 will not be very useful for you.
Now, there is another associated methylation problem with your PEMT mutation. PEMT is normally involved in using SAM to convert phosphatidylethanolamine to phosphatidylcholine. Now this could be seen as an advantage as you can't use SAM and you would think that this would put less strain on your SAM, BUT you need to make phosphatidylcholine (PC) for you lipids in your cell membranes. An alternative pathway is to make PC from choline. In this case however, you will sacrifice your choline, which is used in making acetylcholine, which is one of your most important neurotransmitters. To overcome this, you will need to have lecithin which is basically phosphatidylcholine. It comes from eating eggs.
The other major snp you have is in MAO. This is the most common double mutation seen in CFS and ASD. You need MAO to break down dopamine, nor-epinephrine and epinephrine. You can find out how bad this is by using Dr Google to look at the side effects of MAO inhibitors. It is pretty bad and curiously it is very similar to many of the symptoms that are listed on the B12 deficiency symptom list that you can see at http://b12oils.com/deficiencyfrm.htm If you fill out the form I can let you know which of the symptoms may be entirely due to MAO. To overcome this you need to supplement with lots of vitamin B2, BUT you need to have an active thyroid function to do this as you can't turn B2 into FAD and FMN if you thyroid is not working well.
My suggestion, you need 5MTHF and folinic acid if you can get it. Split the doses so that you get a smaller dose 2 x per day.
You need to sort out your thyroid function as many of the CFS like symptoms are due to low FAD. You thus need to take vitamin B2 and have normal thyroid. The fact that you reacted so strongly suggests that you are a bit out of whack. You also need it to help MTHFR, MTRR, MAO, and DAO and NOS. Oh FAD is also in the one enzyme that is common in CAC and your eletron transport chain. You won't get good energy transfer if you are low in vitamin B2.
If you have found that the sub-lingual AdoB12 was working then you should do well on the Ado/MeCbl mix.
Keep up the vitamin D3 and sun-baking. The higher the levels the better. Oh and I did find VDR Taq mutation, which means that you have trouble keeping vitamin D3 in your body, so the effect of low vitamin D3 will be worse for you.