• Phoenix Rising needs funds to operate: please consider donating to support PR

MTHFR homozygous but can't take B supplement - help needed

Kitsune

Senior Member
Messages
136
Likes
57
Hi - I've recently discovered that I am homozygous for the MTHFR polymorphism. I have started seeing a functional medicine practitioner over the internet who is advising me to start a methylated supplement by Klaire Labs with 1,000mcg methylcobalamin, 800mcg methylfolate, 30mg riboflavin, 15mg P5P, 600mg TMG. I have tried smaller and smaller doses but am overstimulated on each one. Today I tried taking 1/32 of a capsule titrated in water to a quarter, so a 1/128 of a dose - but am still getting symptoms of overstimulation (chest pain, stomach ache, anxiety).

It feels like this is all I've got left to try? I've had adrenal problems for years and am very sick with them. I take other supplements that help - vitamin C, magnesium, liposomal glutathione, zinc, fish oil and some herbs. But I really went downhill this past summer when I stopped my methylated B50 supplement to see if I felt better without it. 2 weeks later I knew I'd made a mistake, but my body would not allow me to take it again, even in small doses. The only thing I've been able to successfully reintroduce lately has been a very weak liquid methylated B-supplement, Biocare Liquid Methyl B Complex, at half a dose. It contains tiny amounts of the Bs, including 50mcg of folate at that dose. While it's almost nothing, I feel better with it than with nothing at all. But I can't seem to get up to the full dose or I get the same overstimulation problems.

I went through something similar earlier in the year - I tried an elimination diet because I have histamine intolerance, and have never been able to add back many of the foods I'd previously tolerated. I can now only eat about 20, though they are healthy Paleo.

What I'm trying to understand is why I've suddenly become reactive to things I used to be able to tolerate, such as healthy foods and my B supplement (it was Swanson). I'm trying to get my body to accept some starting dose of the new methylated supplement, however small, because it feels like that's what I need? Am I wasting my time? Should I tweak it or try something else?

Any advice would be much appreciated! I've tried many times to google reactivity to supplements and food and can't seem to get anywhere.
 
Last edited:
Messages
42
Likes
58
Hi Kitsune, sorry your struggling, it's very difficult at the beginning. When I first started I had many horrible start-up and heavy metal toxicity symptoms. I agree with MT, I started with the hydroxycobalamin and yes I used the folate with it as well as TMG. I went slow, took as much as I could handle and over the course of years I was able to add methylcobalamin and more folate into the mix and now, I no longer need to use the hydroxycobalamin and only use methyl b12. I also used Acetyl-L-Carnitine from the beginning as it really helped my energy and brain fog.

If you're doing methylation, don't forget about potassium and other electrolytes. You might need any of the following if you are firing up your methylation "circuitry" and creating a refeeding situation in your metabolism: potassium, calcium, magnesium, sodium, phosphorus, copper, zinc, boron, iodine, molybdenum, selenium, Omega 3, vitamin C, vitamin D. For me, chest pain is often a symptom of potassium or calcium deficiency.

The threads on this forum contain encyclopedias worth of knowledge and experiences from others who've tried methylation protocols and have been through any start-up symptom you can imagine. When I started this, I had a lifetime worth of mercury, toxic copper, aluminium, viral infections, liver toxicity etc. All of this starts to resolve the very minute you're methylation kicks in and it can be extremely unpleasant.

Early on, any time I was able to ramp up my methylation and raise my glutathione levels, mercury and other toxins would start to mobilize and I would feel terrible anxiety, depression, heart palpitations, brain fog and fatigue. I use coffee enemas which were tremendously helpful. I also realized quite later on in the process that riboflavin was critical for me due to the homozygous MTHFR 1298 SNP that I have.

Since you mentioned your doing Paleo, one thing that recently happened to me was a sodium deficiency. I was taking a lot of potassium and eating no processed foods and got hit pretty hard with fatigue and constantly feeling cold. Turns out I need more sodium as potassium is antagonistic to sodium and I wasn't getting enough with my paleo diet. This website has been very useful for me to help figure out deficiency and overload symptoms for various vitamins and minerals: https://acu-cell.com/index.html
 
Last edited by a moderator:

Kitsune

Senior Member
Messages
136
Likes
57
Hi Kitsune, sorry your struggling, it's very difficult at the beginning. When I first started I had many horrible start-up and heavy metal toxicity symptoms. I agree with MT, I started with the hydroxycobalamin and yes I used the folate with it as well as TMG. I went slow, took as much as I could handle and over the course of years I was able to add methylcobalamin and more folate into the mix and now, I no longer need to use the hydroxycobalamin and only use methyl b12. I also used Acetyl-L-Carnitine from the beginning as it really helped my energy and brain fog.

If you're doing methylation, don't forget about potassium and other electrolytes. You might need any of the following if you are firing up your methylation "circuitry" and creating a refeeding situation in your metabolism: potassium, calcium, magnesium, sodium, phosphorus, copper, zinc, boron, iodine, molybdenum, selenium, Omega 3, vitamin C, vitamin D. For me, chest pain is often a symptom of potassium or calcium deficiency.

The threads on this forum contain encyclopedias worth of knowledge and experiences from others who've tried methylation protocols and have been through any start-up symptom you can imagine. When I started this, I had a lifetime worth of mercury, toxic copper, aluminium, viral infections, liver toxicity etc. All of this starts to resolve the very minute you're methylation kicks in and it can be extremely unpleasant.

Early on, any time I was able to ramp up my methylation and raise my glutathione levels, mercury and other toxins would start to mobilize and I would feel terrible anxiety, depression, heart palpitations, brain fog and fatigue. I use coffee enemas which were tremendously helpful. I also realized quite later on in the process that riboflavin was critical for me due to the homozygous MTHFR 1298 SNP that I have.

Since you mentioned your doing Paleo, one thing that recently happened to me was a sodium deficiency. I was taking a lot of potassium and eating no processed foods and got hit pretty hard with fatigue and constantly feeling cold. Turns out I need more sodium as potassium is antagonistic to sodium and I wasn't getting enough with my paleo diet. This website has been very useful for me to help figure out deficiency and overload symptoms for various vitamins and minerals: https://acu-cell.com/index.html
Wow, that's so incredibly helpful, thank you! I've printed it out to refer to. It's also helpful to know that there will probably be detox symptoms, though I was prepared for those. I hope I don't have to juggle things with all those metals, but one step at a time.

Years back, when my body was able to take more abuse, I did try a version of a methylation protocol here with methylcobalamin and folate. I couldn't take more than 1000mcg of the methylcobalamin without going into an insatiable need for potassium, like pill after pill of it. It was really frightening, so I stopped - I never felt better using that form of B12 as it was (or the adeno form). And always with the B complexes I've taken, they've both helped and hurt me in a way - something was always 'off'. I'm pretty sure now that I don't tolerate methylcobalamin well. Can I ask when you realized you could, and should, switch back to that form yourself?

I'm used to balancing electrolytes and have a lot of Himalayan sea salt throughout the day, so hopefully that won't be a problem. Also eat a lot of sweet potato, which is full of potassium. And I supplement magnesium. Calcium may be a bit tricky - I can't supplement it, it makes me feel bad. But I can always have it in something like a glass of milk if I feel I need it.

If the hydroxycobalamin works, I'm pretty sure I'll need to be taking folate with it straight away. Will then also look at TMG and ALCAR, thank you for the advice. I had some kind of HPA-axis crash last September and have been dealing with anxiety, depression, and adrenal symptoms that have made every day a struggle, so it's good to have some hope. My son is also homozygous for MTHFR and has troublesome symptoms, though he's only 17. I'm hoping to see myself as a trailblazer for us both, but I haven't blazed much of anything yet, just shed a lot of tears.

My new supplements should come tomorrow and I'll try them Sunday morning, then will update. Thanks again for the help! x
 

MTpockets

Senior Member
Messages
202
Likes
580
Location
AZ, USA
What alele are you? If it is the c677t, then you may want to avoid methylcobalamin for good. My girls are homozygous for that and do NOT tolerate that or any type of b complex. They take strictly hydroxy and the methylfolate. If their b12 isn't considerably higher than their folate they get anxiety symptoms. The folate drains the already low b12 when it starts working. A good place to get info is http://mthfr.net/about/dr-lynch/ I don't use his supplements, but I do like his protocol. I have tried several and his suits my family the best. We cover the whole range for MTHFR. Good luck!
 

Kitsune

Senior Member
Messages
136
Likes
57
What alele are you? If it is the c677t, then you may want to avoid methylcobalamin for good. My girls are homozygous for that and do NOT tolerate that or any type of b complex. They take strictly hydroxy and the methylfolate. If their b12 isn't considerably higher than their folate they get anxiety symptoms. The folate drains the already low b12 when it starts working. A good place to get info is http://mthfr.net/about/dr-lynch/ I don't use his supplements, but I do like his protocol. I have tried several and his suits my family the best. We cover the whole range for MTHFR. Good luck!
Yes, that's my alele and my son's. It's really heartening to hear that this regimen works for your girls - I'm going to try to start it tomorrow! Bearing in mind that we're all different, just so I can get a rough idea of where to aim, what kind of ratio of B12 to folate to you use, and what doses? Have you tried TMG or ALCAR or any other kinds of methyl supplements or B vitamins, or do you find that the B12 and folate work OK for you?

And thanks - I'm familiar with Ben Lynch. His supplements are good, and handily specialized for methylation. Still working my way through his site :)

Added in edit: I've tried 200mcg of hydroxycobalamin and 100mcg of methylfolate today. It sounded like a good place to start? Possibly too high a dose, though there was 50mcg of folate in the low-dose liquid B I'd been taking and I was used to that. The depression and anxiety are troublesome today but at the same time I can feel that my body is glad it's not being toxified by methylcobalamin that it can't handle. I take it that start-up symptoms are fairly common?

I hope you don't mind all the questions. I made the mistake of revisiting some of Fredd's posts here and they've always terrified me. I hope this process never gets anything like that complicated for us.
 
Last edited:

MTpockets

Senior Member
Messages
202
Likes
580
Location
AZ, USA
So for my girls I had them start on just the hydroxy. Ben Lynch recommends building up your supply of b12 before you even introduce the folate. I kept them on strictly b12 for a full month. They take an insane amount. But they seem to need it. They take two capsules of 2,000 mcgs a day. If they take more than that they start having anxiety, if they take less, they start having anxiety.( B12 has a direct influence on nuerotransmitters, so it is important to find your personal sweet spot. ) Also if they are taking too much it changes the color of their urine because it is eliminated so quickly.

After they had been on the hydroxy for a month I started them on a quarter of a 400 mcg capsule of folate. We very slowly worked our way up to one full 400 mcg capsule a day. That is all they take. It is 100% of your DV and it is 100% bioavailable for your body. As well as you get 30% of whatever you eat in your food. We eat a lot of legumes, pulses, and greens at our house so that is a decent amount.

We have trialed several other b vitamins but they rock the boat drastically so we don't do anything besides b12 and folate. They eat a lot of fermented dairy and fresh beef, which has very bioavailable b vitamins in it, so I feel confident they are getting everything else through their diet.

I'm not a Dr. and all I have is my own family's experience. My entire family has variations of MTHFR and we aren't treating everyone. My sons have the A1298 alele, but that means they absorb 75-ish% of all the folate they eat. So I make sure they eat plenty. I don't treat them. They don't have a period every month, they won't ever be pregnant, and I'm not worried. They don't have anxiety and are in great health. If they ever lost a significant amount of blood or had a general anesthesia, I would probably supplement them for a while to replace what was lost.

My husband and I are both heterozygous for both aleles. I treat and he doesn't. I didn't start treating until four children and several major surgeries had pretty much depleted me. Every alele has a different severity with the c677t being the worst. You only absorb 30% of the folate you eat. If you add in a monthly blood loss you will be low in no time. General anesthesia and dental gas can also deplete you dangerously quick. But in my experience even more than general health, it has a major influence on the nuerotransmitter balance. If my girls forget to take their vitamins in the morning I can tell by noon. It makes that much difference.

Sorry this is so long. Hope it helps. Let me know if you have anymore questions.
 

MTpockets

Senior Member
Messages
202
Likes
580
Location
AZ, USA
A quick mention about start up symptoms... I think it all depends on the person and possibly the situation. I did everything out of order when I was starting. I took folate before the b12, I was on the wrong type of b12 for my body, I had years of anemia to correct the list of mistakes goes on and on. I had major "start up symptoms" By the time I got my girls tested I had learned a crazy amount, mostly by trial and error. So I started them the right way. It was a little rough for a few weeks mentally until they found their sweet spot for the b12, but they have never needed anything else as far as supplements go. They do take magnesium to keep their elimination regular, but I think that is an issue caused by excessive antiobiotics from when they were small. We are working on that.

They never had start up issues. I can't help but wonder if the people who have major start up symptoms might need a different approach or need to address other issues before they try to tackle their MTHFR. I know it can sound crazy complicated, but I'm not sure it needs to be. But what do I know?
 
Messages
42
Likes
58
I agree MT, I think it's all very individual. I have two CBS mutations, one of them homozygous, and multiple GAD SNPs so I had to address that first by getting my sulphites, ammonia and glutamate under some semblance of metabolic control otherwise anything I tried just gave me terrible arrhythmia and palpitations and made me unbearably anxious and obsessive. As soon as I did that I was able to start getting rid of the mercury, cadmium and copper toxicity.

I also have a bunch of SNPs in the liver detox and sulfation pathways so I had to take it slow, I did several dozen weekends of Cutler ALA chelation, lots of coffee enemas and I used NAC and glycine for several years. Luckily, my mercury level wasn't that high as I had no amalgam fillings.

I also corrected my hypothyroidism by doing a couple of years of high dose iodine protocols. I had to do salt pushes with that for bromine elimination as I worked in an industry that exposed me to bromine based fire retardants for a while.

I didn't really start serious methylation protocols with methyl b12 and folate until I had those things well under way and even then, for years, any time I increased my dose of methyl b's, I would need to take tons of molybdenum because my CBS would up regulate and I would dump copper and mercury as soon as I got my methylation ramped up.

In addition to the MTHFR SNPs I also have multiple SNPs for MTRR, MTR and MTHFS, DHFR, DAO-A, BMHT and COMT so my b12 metabolism is completely screwed up, I can't tolerate even trace amounts of artificial folic acid or folinic acid and methyl donors can push my adrenaline sky high.

For me, I think as a full grown adult who has spent a significant portion of their life severely undermethylated with a b12 and folate deficiency, I had no choice but try to ramp up methylation to heal my neurology. High dose methyl b12 therapy has been the most effective thing so far for me.
 

Grigor

Senior Member
Messages
453
Likes
1,017
Location
Amsterdam
Very interesting to read your story about the sensitivities to the smallest amount of supplements. It mirrors mine completely. Also when I forget to take something and eat or swallow it in the afternoon it kicks in hard and will be intolerant from then on.

If you find a solution let me know please!
 
Messages
42
Likes
58
There really isn't a solution that I can offer you because the solution is to do whatever you can handle. Basically, you need to fix your methylation as fast as you can based on your individual tolerances, genetics and epigenetics. Healing from anything takes time and usually comes with some amount of suffering unfortunately.

In my humble opinion, if you have inborn or epigentic problems with b12 and folate metabolism that you have lived with for a portion of your life, to the point where it causes symptoms, at some point you're probably going to need to do advanced methylation protocols with high dose methylcobalamin and folate to heal your neurology. You may need more than this as well. Freddd has recently found out that lithium was a huge missing factor for him in his recovery and that last piece has allowed him to reach homeostasis. The learning and tweaking really never stops for people like us.

With all of the SNPs listed above even the COMT, I'm currently taking 60 mg (60,000 mcg) per day of sublingual methylcobalamin and 25-35 mg of L-methylfolate and I've never felt better although, it took me a long time and a lot of suffering to get here. I'm going to try the transdermal b12 oils next because I'm hoping they work better than the sublingual.

- "He who learns must suffer. And even in our sleep pain that cannot forget falls drop by drop upon the heart, and in our own despair, against our will, comes wisdom to us by the awful grace of God. " - Aeschylus
 

Kitsune

Senior Member
Messages
136
Likes
57
A quick mention about start up symptoms... I think it all depends on the person and possibly the situation. I did everything out of order when I was starting. I took folate before the b12, I was on the wrong type of b12 for my body, I had years of anemia to correct the list of mistakes goes on and on. I had major "start up symptoms" By the time I got my girls tested I had learned a crazy amount, mostly by trial and error. So I started them the right way. It was a little rough for a few weeks mentally until they found their sweet spot for the b12, but they have never needed anything else as far as supplements go. They do take magnesium to keep their elimination regular, but I think that is an issue caused by excessive antiobiotics from when they were small. We are working on that.

They never had start up issues. I can't help but wonder if the people who have major start up symptoms might need a different approach or need to address other issues before they try to tackle their MTHFR. I know it can sound crazy complicated, but I'm not sure it needs to be. But what do I know?
Wow, I didn't know there were so many new posts here; I was amazed when I came back. Lots to absorb. But I wanted to say you do know a lot, and in fact I think you may well have saved me from some real panic and more mistakes. I was convinced I needed at least a little folate, but the 200mcg hydroxy / 100mcg folate was killing me after just 2 days - sudden brain fog, depressive symptoms worsening. I've read what you wrote here about how folate can initially make B12 deficiency symptoms worse unless you load up on the B12 beforehand, so I'm cutting the folate out for myself and my son. He was fine with it, but he may have ended up not being, and we agreed we're going to do this together (though of course his way will very probably end up being different from mine). Thank you for sharing that information with me, truly.

So I've always taken a B-complex before, though I don't know how much good it ever did me. I feel brighter with just 200mcg of hydroxy, but it's been giving me stomach upset and a dry mouth and I'm not sure why. Maybe I just need to get used to it. I've prepared the way for this as well as I could - taking glutathione, electrolytes sorted, healthy (if limited) diet, other support supplements in place - vitamin C, fish oil, zinc, etc. I'm not sure how much benefit I ever got out of B-complex supplements; as you say, that could be complicated, and they might not be necessary at all.

I do hope it doesn't get crazy complicated for my son and me. I really like the sound of what you did with your girls and don't want to take more of anything than I need. Like you, I've gone through so much trial and error and pain to get here. I just wish I wasn't so sick starting out, because that will make the inevitable bumps harder, like it has these past few days. But the only way through is forward.

One question - did you ever try having a dose of your methyl supplements at lunch or in the afternoon? Some protocols recommend that. I am more reactive to B vits at that time of day but I also find that I feel better in the morning - more energy. Maybe I'll see if I can make that work this time.

It doesn't help that I was glad to find a good functional medicine practitioner, only to discover he takes a bit of a one-size-fits-all approach and seemed to think my failure to tolerate his recommended supplement with methyl B12, folate, B2, B6 and TMG must mean I need my system detoxifying, etc. I don't believe I am toxic to that degree, and so here I am, back to researching and trial and error on my own. Though he did interpret my 23 and Me genetics for me, and has had me take an organic acid profile test, which looks like it might end up being a good diagnostic tool when the results are in.

I'll update this thread with how I'm doing, but I admit I'm scared a lot of the time. I get SAD and it's worse this year than it's ever been - this country (UK) is so dark and cloudy in the winter. There's never any knowing whether I'm on the right path to healing, what I need to do next, what I need to take, what my body will throw at me. But thanks to you, I've got hope and some reassurance that I may finally be doing the right thing :)

Added in edit: Ugh today's been hard too! I was previously on 50mcg a day of folate and may need to keep that in. Finding a balance is so hard. Can I ask what your startup symptoms were like?⁶
 
Last edited:
Messages
42
Likes
58
Hi Grigor, sorry I misunderstood. For the intolerance to artificial folates I eat a strict paleo diet. No grains, no dairy, no sugar and almost no processed food of any kind. I also have celiac disease so this diet has helped me almost as much as the supplement regime.

Thank you. I was more referring to the intolerance but the methylation is a thing I'll focus on from now on for sure!
 
Messages
42
Likes
58
Hi Kitsune, hydroxycobalamin is very safe and 100 mcg of folate is also low enough to be very safe. If the supplements are causing that much mental suffering, e.g. anxiety and depression, you could look at your 23 and me and look for SNPs that affect neurotransmitter production. These would be COMT, GAD, DAOA, MAOA, TPH and the ones in the tryptophan to serotonin pathway. These will affect how you feel when taking these supplements and there are ways to compensate for that.
 

MTpockets

Senior Member
Messages
202
Likes
580
Location
AZ, USA
I split my own dose into morning and afternoon. My girls respond better to all in the AM. But try it and see. It is a game of trial and error. My start up symptoms were horrible anxiety, insomnia, and restless muscles. I had hair loss as well. But like I said I did everything wrong and had several major issues that needed fixing that I wasn't aware of. For the SAD do you take vitamin d? My daughter has recently moved to a place that gets way less sun and she started taking vitamin d. She is tolerating it really well.

Regarding stomach upset b12 is one of the things responsible for stomach acid production. You may want to take it with a little yogurt or something. And don't take it on an empty stomach. I always take mine with meals. If you have SIBO the stomach thing may be die off. They do have the tablets that dissolve under your tongue if you want to bypass your stomach altogether. I know it seems overwhelming, but go slow, only change one thing at a time and listen to your body. Just because it works for one person, doesn't mean it will work for you. Hang in there.
 
Messages
11
Likes
18
Hi Kitsune, sorry your struggling, it's very difficult at the beginning. When I first started I had many horrible start-up and heavy metal toxicity symptoms. I agree with MT, I started with the hydroxycobalamin and yes I used the folate with it as well as TMG. I went slow, took as much as I could handle and over the course of years I was able to add methylcobalamin and more folate into the mix and now, I no longer need to use the hydroxycobalamin and only use methyl b12. I also used Acetyl-L-Carnitine from the beginning as it really helped my energy and brain fog.

If you're doing methylation, don't forget about potassium and other electrolytes. You might need any of the following if you are firing up your methylation "circuitry" and creating a refeeding situation in your metabolism: potassium, calcium, magnesium, sodium, phosphorus, copper, zinc, boron, iodine, molybdenum, selenium, Omega 3, vitamin C, vitamin D. For me, chest pain is often a symptom of potassium or calcium deficiency.

The threads on this forum contain encyclopedias worth of knowledge and experiences from others who've tried methylation protocols and have been through any start-up symptom you can imagine. When I started this, I had a lifetime worth of mercury, toxic copper, aluminium, viral infections, liver toxicity etc. All of this starts to resolve the very minute you're methylation kicks in and it can be extremely unpleasant.

Early on, any time I was able to ramp up my methylation and raise my glutathione levels, mercury and other toxins would start to mobilize and I would feel terrible anxiety, depression, heart palpitations, brain fog and fatigue. I use coffee enemas which were tremendously helpful. I also realized quite later on in the process that riboflavin was critical for me due to the homozygous MTHFR 1298 SNP that I have.

Since you mentioned your doing Paleo, one thing that recently happened to me was a sodium deficiency. I was taking a lot of potassium and eating no processed foods and got hit pretty hard with fatigue and constantly feeling cold. Turns out I need more sodium as potassium is antagonistic to sodium and I wasn't getting enough with my paleo diet. This website has been very useful for me to help figure out deficiency and overload symptoms for various vitamins and minerals: https://acu-cell.com/index.html
Hello. I wanted to send you a message but I'm new here for 2 weeks and still don't see any "message" button. I too have MTHFR 1298 homozygous and saw some of your messages about your experience. I wanted to ask, how did you know that you needed more molybdenum to help with heavy metals burden? And how you felt that it works, your potassium need decreased? Please, share your experience. Almost all of methylation supps made me worse, so now I only take Alpha lipoic acid every 3 hours and potassium (12+g, yeah it's terrible). I also just checked my thyroid hormones, it looks like hypothyroidism and I have high antibodies (guess it's because of heavy metals)