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No response from high dose B12 & Methylfolate...what am I missing?

Messages
87
I have spent the last couple of months researching and going through my understanding of methylation and my supplement forms/dosing with a fine tooth comb and my conclusion is I am still missing SOMETHING.

The crux of the problem seems to somewhat center around the fact that I don't respond to B12 or Methylfolate hardly at all. I feel nothing with 30mg of MeCbl (Jarrow), 50mg of AdoCbl (Source Naturals) or 30mg of Methylfolate (Solgar). FWIW - I am taking the B12 sublingually as intended.

I've taken between 10-30mg of Methylfolate a day for the last 3-4 months with negligible effect. To be fair though I didn't realize until somewhat recently that I needed to take more MeCbl than I took folate, and since I never felt it one way or another when I took MeCbl I wasn't always consistent with taking a high enough dose of MeCbl.

My blood pressure and pulse have stayed almost frustratingly stable 120s/80s with a 75-85bpm pulse. With no need for supplemental potassium.

Couple of factors
1.) Last time I actually had my serum levels of B12 checked, several years ago, I was off the charts (>1999) and my folate levels were similarly about double the upper limit. So there is something potentially off there

2.) A couple of weeks ago I realized, when I went back and looked after reading about methylation roadblocks, that my lithium levels in my hair test were below the lowest value on the test, so I added the 10mg of lithium.

3.) My dad has done virtually the exact same things and has an almost identical response, where as my mother can take 400mcg of methylfolate and definitely feels it. So there could possibly be some genetic factor at play.

Current Supplements:
Vitamin A - 50,000 IU
Vitamin D3 - 8,000 IU
Vitamin E - 400 IU

Vitamin B1 Benfotiamine - 600mg
Vitamin B2 (sublingual FMN) - 18.6mg
Vitamin B5 (Pantethine) - 450mg
Vitamin B6 (P5P) - 100mg
Biotin - 30,000mcg

Zinc Picolinate - 100mg
Magnesium Glycinate - 600-800mg
Selenium - 200mcg
Molybdenum - 2000mcg
Manganese - 50mg
Boron - 9mg
Kelp - 1800mg
Lithium Orotate - 10mg

TMG - 2,400mg
Taurine - 2,000mg
Creatine HCL - 2.5g
MSM - 8g
Vitamin C - 500mg
DIM - 100mg
L-Carnitine Fumerate - 1000mg​

I could potentially see not responding to B12 with sky-high serum levels, but not feeling anything from up to 30mg of methylfolate taken over an extended period has me perplexed.

Is there anything you can see that I would possibly be missing?
 
Last edited:

aaron_c

Senior Member
Messages
691
Those are really high levels of methylfolate and methylcobalamin. I'm a bit concerned that, if you do find that last crucial ingredient, you'll have a pretty dramatic response that could, particularly in terms of potassium, get dangerous.

That said, I see you don't list carnitine. I know Freddd regarded carnitine as an essential part of his protocol. As I recall, he seemed to think that different people would find different forms of carnitine to be the most beneficial. The forms I know of are L-Carnitine, Acetyl L-Carnitine (ALCAR), and Carnitine Fumarate, so you might want to try some or all of those.
 

mattie

Senior Member
Messages
363
There are many PWME who do not respond to this approach at all. I am one of them. It certainly does not mean you are doing it wrong or that you are missing something.
 
Messages
87
Those are really high levels of methylfolate and methylcobalamin. I'm a bit concerned that, if you do find that last crucial ingredient, you'll have a pretty dramatic response that could, particularly in terms of potassium, get dangerous.

I know what you mean. I had a similar experience a couple of years ago when I was working on methylation and finally got things to "click" and started to overmethylate. Fortunately, I have a much better understanding of how to reign it in now.

That said, I see you don't list carnitine. I know Freddd regarded carnitine as an essential part of his protocol. As I recall, he seemed to think that different people would find different forms of carnitine to be the most beneficial. The forms I know of are L-Carnitine, Acetyl L-Carnitine (ALCAR), and Carnitine Fumarate, so you might want to try some or all of those.

Good catch, I am actually taking 1000mg L-Carnitine Fumarate and I updated my above list to reflect that.

There are many PWME who do not respond to this approach at all. I am one of them. It certainly does not mean you are doing it wrong or that you are missing something.
Many patients don´t respond at all, probably because methylation has nothing to do with their disease

I could understand not responding to additional B12 if levels are sufficient, but its that fact I don't respond to the methylfolate (especially at such a high dose) that has me perplexed.
 

PatJ

Forum Support Assistant
Messages
5,288
Location
Canada
I feel nothing with 30mg of MeCbl (Jarrow)

There were a lot of unhappy people several years ago when Jarrow changed the formula for their MB12 and it became ineffective for many individuals. If Jarrow is still using the same formula then it might explain why you don't notice anything.

Freddd recommended Enzymatic Therapy as the best quality in an oral supplement but you would need to take a bottle per day at your current dose since they only come in 1mg tablets, 30 per bottle. Country Life has 5mg tablets that were also recommended and would be more economical.
 
Messages
9
@Bluelude1

Did you find what were you missing? Cause I'm currently in the similar situation. I'm having B12 deficiencies despite trying high doses of Methylcobalamin. I have tried 40 000mcg sublingually and I also injected today 5000mcg of Mecbl but it doesn't help at all.
 
Messages
9
Thanks for the advice. I will try to experiment with b6. Is methionin enough? Shouldn't I take S-adenosylmethionine?
 

Learner1

Senior Member
Messages
6,305
Location
Pacific Northwest
Methionine and homocysteine recycle each other. Most people have issues with not enough folate, B12, etc. and have too high homocysteine. Occasionally, as in my case, when merhylation is running fast, one can run short of methionine. The symptons I got were depression and edginess. My homocysteine was 3, when ideal would be 6-8. Adding methionine raised homocysteine to 6 and my unpleasant symptoms went away.

Pyridoxal-5-phosphate is a good form of B6.

Make sure you have sufficient amounts of the other cofactors as well.

Good luck!
 

Moof

Senior Member
Messages
778
Location
UK
Also, if you have an insufficient response to methylcobalamin, it might be worth trying hydroxocobalamin if it's available in your area.

It's been the most successful injectable for me; I've no idea why, but I just respond better to it. By pairing it with plenty of greens and a modest dose of methylfolate a couple of times a week (100% RDA), I get all the gains without any jitteriness and fragility. It also happens to be much cheaper than methylcobalamin in Europe – it's the form of B12 most often prescribed for pernicious anaemia, meaning there are economies of scale in production – so I'm not complaining! :)