My experience of B12/methylation issues. Looking for advice/discussion please

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Sorry for the long post, I wanted to give my full history. Thanks to anyone that reads it. My questions are at the end if you want to skip.

History

First of all, I suffer from the C677T mutation of the MTHFR gene. I have a few other mutations that may affect methylation but I don't understand the significance of them. I also suffered from some serious gut issues (IBS/IBD and/or leaky gut) for some years, but happy to say that I seem to have resolved that now so I won't go into it.

I have always had difficulty sleeping (average time to fall asleep 3-5 hours) and I never feel rested, no matter how much sleep I get. For most of my adult life I have always felt tired and low energy and have difficulty finding the energy to do things because I feel so wiped out all the time. I am male, 34 years old.

In early 2019 I went to the doctor complaining about the tiredness (not for the first time). At various times I've previously been diagnosed with depression, and insomnia (both true). This time they did some blood tests and discovered that I had very low levels of B12. They prescribed B12 injections, and the difference was incredible! I realised I had lived most of my life with the energy levels of an 80 year old, and I was just so used to it that I didn't realise I wasn't supposed to be like that. Suddenly I had the energy to do things, I felt happier, more motivated, didn't feel like I was going to collapse whenever I did exercise.

I wanted to know why I was deficient. I am an omnivore and eat plenty of meat, fish, eggs and dairy, so I shouldn't be, which to me suggested an absorption issue. But unfortunately the doctors in the UK are not very good and basically didn't want to give me any more attention. They just said to get tested again after a year. Because of Covid lockdowns, in 2020 the doctor locked their doors and switched off their phone lines so I couldn't get treated.

By April 2021 I felt like I was dying. I can't stress enough the unbelievable fatigue I felt. It was like all the energy had been drained from me by a vampire. That feeling when you have the flu and feel overwhelming debilitating tiredness - I felt that 24 hours per day. But couldn't sleep regardless. I couldn't exercise. I continually felt like I was going to collapse or faint.

Worst of all, my brain wasn't working properly. I couldn't think. I couldn't remember things. In fact I had completely forgotten about the B12 deficiency. It was like I was in a fugue state, just struggling to get through each day. Sometimes all I could do was lie down.

I was struggling to do my job and kept getting called into disciplinary meetings to ask what was wrong with me. They asked me if I was having health issues or personal issues, but I didn't know what to say. I didn't know why I was doing so bad, it was just like my memory didn't work and I couldn't think or concentrate.

I continually tried to get in contact with the doctor, but the NHS is so bad and oversubscribed. The only service available was a text-based service whereby the GP replies with half a sentence of broken English and you can't reply to it. I naively kept getting tested for Covid because I thought there must be something seriously wrong. But it always came back negative.

I continually suffered from digestive issues. It was like my stomach wasn't emptying. I had trouble digesting food, low appetite, frequent diarrhoea, abdominal pains which I thought might have been my pancreas, gall bladder or stomach ulcers.

I kept trying to get in touch with the doctor but very little help was available to me. I was also depressed and suffering all kinds of psychiatric issues, irritability, inability to concentrate, hypersensitivity to everything (smells, noises, light, touch) and really bad tinnitus. I was even having difficulty walking - it was like my brain couldn't work out how to put one foot in front of the other so I had a weird gait.

It was at this point that I found a Reddit thread in which someone in the comments linked to a big thread on this forum, and suddenly I remembered B12. Of course... why did I forget? It's so obvious now. I must have been deficient again. It was more than 2 years since I had the injections.

I contacted the doctor and asked be tested, and they said "yes, you should have been tested again before now". Unfortunately with the waiting times on the NHS, the wait to have a blood test was almost 3 weeks, and then it would be 4-7 days to get the results, and then another 1-2 weeks before I would get the injections.

During that time I deteriorated further. I couldn't do my job any more. I was struggling to do basic things like cooking. When I touched my scalp, clumps of hair would come out. I was having frequent heart palpitations. My tongue was sore and too big for my mouth. I had sores in my mouth. I had dry red scaly patches of skin all around my mouth and nose, and on my arms, torso, feet, pretty much everywhere were patches of red skin that wouldn't heal for weeks or months.

My hands were tingling with pins and needles 24/7 and going numb. My toes had been purple and swollen for a year and I couldn't feel them. My vision was blurry. My brain was barely functioning at all. I couldn't concentrate on anything and didn't know what I was doing from one moment to the next.

Sublingual B12

So I decided I couldn't wait for the blood test, and I was worried about suffering permanent neurological damage. I read up on the posts here and ordered some sublingual methylcobalamin and adenosylcobalamin.

The relief was remarkable. Within a few hours it was like a fog being lifted. I felt energy return and I felt my mind become clear. Over the next few days everything healed - all the sore patches of red skin went away. My tongue stopped being swollen, my hair stopped falling out. After 2 weeks my toes stopped being swollen and returned to normal size (my theory is it was megaloblastic anemia meaning the red blood cells couldn't get into the small capillaries?). The heart palpitations and weird out of sync heart beats also seem to have stopped. My mood improved. I am even falling asleep quicker (1-2 hours instead of 3-5 hours).

When I finally had the blood test, my B12 levels came back OK (about 210pg/100mL). Presumably because the sublingual bioavailable B12 had worked, but this meant they didn't give me any injections or any further possibility of treatment or discussion with a doctor.

I have continued to take the sublingual B12 every morning (about 2400 mcg, but I doubt I'm absorbing all).

Whilst the energy levels and all other symptoms have improved a lot, the tingling and numbness in my hands remains and in fact has seemed to be getting worse. From reading on this forum, I'm wondering if that is part of the healing process?

My questions:

* Should I keep taking the sublingual B12? Am I wrong to keep taking it even though my blood test came back with acceptable B12 levels?
* Should I take an even higher dose? I read that it's virtually impossible to overdose on B12.
* Should I spread the dose out throughout the day instead of taking it all in the morning?
* Is it important to take anything else? I take methylfolate as well because of my genetics, and I also take a high dose of thiamine and sometimes riboflavin.
* Should I avoid NAC? I was taking that earlier in the year and I'm wondering if it precipitated my rapid decline due to using up the cobalamin. I've read mixed things about it, with some people saying it protects cobalamin, and other people saying it causes it to be excreted.
* Will the numbness and shakiness/clumsiness of my hands get better eventually? It's the thing I'm most worried about.
* Do you think I have caused permanent damage to by brain or body by going untreated for so long?

I would appreciate any advice about what I should or should not be doing.
 

nerd

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* Should I keep taking the sublingual B12? Am I wrong to keep taking it even though my blood test came back with acceptable B12 levels?
I think it's only an issue when the results come back too high.

Should I take an even higher dose? I read that it's virtually impossible to overdose on B12.
For an average patient, it's impossible. ME is always a separate story, no matter what it concerns.

* Should I spread the dose out throughout the day instead of taking it all in the morning?
If you experience side effects from it, you might consider it.

* Is it important to take anything else? I take methylfolate as well because of my genetics, and I also take a high dose of thiamine and sometimes riboflavin.
I've read different experiences with folates and I think it depends on the genotypes and "ME types" how the folate metabolism is balanced and if it makes sense for you. I might already have asked this in another post, have you tried TMG or SAMe?

B12 might contribute to the already existing intracellular calcium, sodium <=> potassium, phosphorus imbalance. So potassium salts might be preferrable over sodium salts. This only affects serum levels, unfortunately, and the impact on intracellular levels is limited due to the dysregulation of the respective cell membrane pumps. There are drugs that can alleviate this dysregulation, but I can't give personal advice.

* Should I avoid NAC? I was taking that earlier in the year and I'm wondering if it precipitated my rapid decline due to using up the cobalamin. I've read mixed things about it, with some people saying it protects cobalamin, and other people saying it causes it to be excreted.
My personal experience with NAC is positive, but only with high quality and fresh NAC that doesn't smell sulfuric. I'm currently using Thorne with good experience.

* Will the numbness and shakiness/clumsiness of my hands get better eventually? It's the thing I'm most worried about.
When my ME was worse, I also had shakiness, but it's mostly gone now. A certain level of clumsiness remains though. I can't tell what really made the difference. Eliminating sugar might have played a role. Or reducing coffee and glutamate sources in my diet. Or avoiding iodine in my supplements (due to dysregulated thyroid). Or reducing sodium in my diet.

* Do you think I have caused permanent damage to by brain or body by going untreated for so long?
In aging terms, I think ME patients age faster, and this includes more brain damage. A "real" treatment of the causality hasn't been determined yet, so the difference between untreated and treated probably isn't so large.

I would appreciate any advice about what I should or should not be doing.
We can't give medical advice, though even medical advice is poking in the dark scientific forest that ME still is. Here is a list of supplements I also take: EPA (omega-3 FA) for heart muscle protection and to protect from oxidative damage, medium-dose Niacin, Huperzine A to improve AChR function, Acetyl-L-Carnitine for fatty acid transport and the nervous system, Phosphatidylserine to improve cell membranes.
 

Pyrrhus

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* Is it important to take anything else? I take methylfolate as well because of my genetics, and I also take a high dose of thiamine and sometimes riboflavin.
Pyridoxal-5'-phosphate (vitamin B6) is often taken along with B12 and folate, since it also participates in the same metabolic processes as B12 and folate.

* Should I avoid NAC? I was taking that earlier in the year and I'm wondering if it precipitated my rapid decline due to using up the cobalamin. I've read mixed things about it, with some people saying it protects cobalamin, and other people saying it causes it to be excreted.
Here's a thread that discusses this question in detail:
https://forums.phoenixrising.me/thr...inducing-b12-deficiency-or-methyl-trap.79380/

* Will the numbness and shakiness/clumsiness of my hands get better eventually? It's the thing I'm most worried about.
Over time, my numbness/weakness (peripheral neuropathy) has slowly improved with B12 and related co-factors. Your experience may vary.
 
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My personal experience with NAC is positive, but only with high quality and fresh NAC that doesn't smell sulfuric.
The NAC I have smells very strongly of sulphur, but I thought that's just what it smells like.
[/QUOTE]

have you tried TMG or SAMe?
I've tried neither. To be honest I don't fully understand their role and was worried about over-methylation due to all the methyl donors I'm taking.
 

nerd

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The NAC I have smells very strongly of sulphur, but I thought that's just what it smells like.
It's supposed to smell like vinegar. Or barely have any smell at all. Only when you open it for the first time, it's natural that some sulfuric gas residues escape, but ideally, there shouldn't be much. The capsule content itself shouldn't smell like sulfur.
 

Judee

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* Should I keep taking the sublingual B12? Am I wrong to keep taking it even though my blood test came back with acceptable B12 levels?
* Should I take an even higher dose? I read that it's virtually impossible to overdose on B12.
* Should I spread the dose out throughout the day instead of taking it all in the morning?
This.

And the reason that I say so is I would first try to duplicate as closely as possible what worked for you the first time before adding anything else into the mix that could "muddy the waters" or make it not work as well for you.

And especially since you said, starting the b12 again resolved some things for you again.
 

Mick

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But unfortunately the doctors in the UK are not very good
Tell me where they are good, name one country when it comes to matters like this or a follow-up in such a seemingly innocuous matter.

When I finally had the blood test, my B12 levels came back OK (about 210pg/100mL)
This is not OK when you consider Japanese normal ranges - 500-1300 pg if I remember correctly so there is still room for improvement, definitely.

Also read this article:
https://advances.augusta.edu/1014

Should I take an even higher dose? I read that it's virtually impossible to overdose on B12.
You should. Your nerves may require a higher concentration (thus greater local availability) in order to heal faster. If a healing process has started it requires more B12 - I think this is obvious. But also you should increase your dose quite slowly, in steps. I used to take 5000 mg daily and I wasn't even deficient (at that time but I was earlier). It is prudent to stop it for like 3-4 days and see if you feel any different. For example 5000 mg daily may be too much and you will be getting nervous after taking it and this 3-4 day break from taking it will allow you to see what is going on.

Should I spread the dose out throughout the day instead of taking it all in the morning?
I see no contrindications. Why stress the body with very high doses at once? They may tell you that it doesn't matter when you take it but it may, who knows. Better be safe than sorry.

Is it important to take anything else? I take methylfolate as well because of my genetics, and I also take a high dose of thiamine and sometimes riboflavin.
The answer to this question is also very simple. If you experienced vitamin b12 deficiency at a young age (as I assume) there must be something wrong with your stomach (or metabolism). If there is something wrong with your stomach then all other nutrients may be malabsorbed. Moreover, your nerves require different nutrients to heal and there may be a lot of healing and it may take years (even though the most severe symptoms are gone). I will not name them here because that would be beyond the scope of this reply and you have to search this forum and google this out. Something like "healing nerve damage b12 deficiency" comes to mind. Of course, a good multivitamin would be a start. Of course, a test for vitamin deficiencies would be a start. I don't know if this is available for you via NHS or you can pay it out of your pocket.
But it's also not like such a test is a definite answer to all your problem as it may not detect some of the deficiencies. Magnesium, omega-3, lecithin, methylfolate, phosphatidylserine - that's what I would take for now and see if they help (they can't hurt) and in the meantime I would look for further answers.

Obviously, you may feel just fine after taking some of them so your solution may be one step away...
But do you still feel tired at all? Maybe simply you need to give nerves some time to heal (while taking some of the supplements)...
 
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The good news is my neuropathy has been gradually improving over the last few weeks. It no longer feels like I'm wearing a glove, and I don't have permanently numb hands. I just get occasional tingling for a few minutes, but much less, and it's becoming less frequent with each passing day. So I think my nerves are healing. I'm very pleased about that.

I'm finding my muscles get extremely sore after exercise. I don't know if that's because previously they had no ability to recover because my body couldn't make new cells, or maybe exercising is putting increased strain on my B12 levels.

This is not OK when you consider Japanese normal ranges - 500-1300 pg if I remember correctly so there is still room for improvement, definitely.
Yes, I was thinking it's pretty borderline. My symptoms were so bad before, I think my doctor should have followed up and done more tests. But I've been left to medicate myself instead.

The answer to this question is also very simple. If you experienced vitamin b12 deficiency at a young age (as I assume) there must be something wrong with your stomach (or metabolism). If there is something wrong with your stomach then all other nutrients may be malabsorbed. Moreover, your nerves require different nutrients to heal and there may be a lot of healing and it may take years (even though the most severe symptoms are gone). I will not name them here because that would be beyond the scope of this reply and you have to search this forum and google this out. Something like "healing nerve damage b12 deficiency" comes to mind. Of course, a good multivitamin would be a start. Of course, a test for vitamin deficiencies would be a start. I don't know if this is available for you via NHS or you can pay it out of your pocket.
But it's also not like such a test is a definite answer to all your problem as it may not detect some of the deficiencies. Magnesium, omega-3, lecithin, methylfolate, phosphatidylserine - that's what I would take for now and see if they help (they can't hurt) and in the meantime I would look for further answers.
I don't know if I have an absorption issue or not. It's certainly possible, because I did have a history of digestive issues and abdominal pains, but it's difficult to say whether they were caused by B12 deficiency or the other way around. Maybe once B12 levels get low enough it becomes harder for the body to absorb it if it can't heal the lining of the stomach any more or produce new parietal cells.

I previously experienced an increase in energy level and mood after eating liver, which to me suggests I am absorbing B12 from food, unless it's some other nutrient responsible - liver is very nutrient dense. It usually only lasted for a day or less.

I thought it might be my genetics which is causing me to have higher requirements for B12. Perhaps some part of the methylation cycle is being driven more, or my high homocysteine levels from MTHFR mutation mean even with adequate dietary levels of B12, I'm still ending up deficient.

Obviously, you may feel just fine after taking some of them so your solution may be one step away...
But do you still feel tired at all? Maybe simply you need to give nerves some time to heal (while taking some of the supplements)...
Yes I think so. The improvement in energy levels was fairly fast after B12 supplementation, but I think the damage to the nervous system takes longer to heal. It could be some weeks or months, and I might consider increasing my dosage because I don't just need normal levels, I need to keep the levels high as they are being used up in healing years of damage.

Once all the neurological issues go away and I have a better response to exercise, I might consider lowering to a maintenance dose.
 
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Have you tried or can you afford b12oils.com? These b12 oils that come in an air tight sealed cylindrical pump supposedly have superior bioavailability and absorption into the blood stream and specifically the brain. This might get your b12 levels into a much better place.

Whenever I've taken b12 over the last 6 years my levels always seem way over the upper limit. So you might want to make sure you've not got anything blocking your b12 absorption. Hence why b12 oils might make a huge difference.

And organic acid test from Genova diagnostics via a neutropath might also help you understand what you're missing and need to address.
 

Mick

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I'm finding my muscles get extremely sore after exercise.
If your muscles are affected then I'd say you shouldn't wait. Nerves - it's a different story and muscles - it's a different story. Why... because muscles, opposite to nerves, are usually very fast to recover - nerves heal quite slow because that's how they evolved - they are not damaged too often. Muscles are damaged every day and have to be able to deal with these damages. So, if muscles are affected - it's a completely different story.

So, you may have another problem / disorder that just showed itself after this problem with B12 def.
Or, such a severe deficiency of B12 impaired the production of different endogenous nutrients which are usually produced by the body.

It doesn't make any sense to wait for an undefined amount of time.
It's better to aggresively start supplementing different nutrients/mitiochondrial coctails.
Whatever bodybuilders take: creatine, protein, vitamins... there should be no problem finding which supplements to take. Also, CoQ10 and mitoQ.