Methyl-Folate worsened shortness of breath, anxiety, irritability

[Tor]

I don't have ME, but this forum is the most helpful resource ever, so I hope it is okay to post here.

My blood test showed that I'm homozygous for the MTHFR mutation - I am 24 years old. This was a huge relief to learn, as my health has been quickly deteriorating over the past few years, and nobody could figure out why. The same thing has happened to both of my brothers, so they are getting tested as well.

My symptoms are:

• Extreme internal anxiety (even though everyone thinks I'm "so calm" on the outside)
• Shortness of breath
• Insomnia (waking up frequently and early)
• Constant tightness / dread in chest
• Extreme irritability at trivial things, especially noises
• Headaches out of nowhere (especially in the middle of the night)

Me and my entire family also have a history of drug / alcohol abuse, although I have completely stopped out of concern for my health. We also have a history of stroke, heart disease, and joint pain.

My doctor prescribed Klonopin to help with the shortness of breath, but it didn't help at all. I remained irritable and anxious, in addition to just feeling exhausted.

After reading as much as I could, I found that Sam-E is a methyl donor and can provide immediate relief to undermethylators. It definitely did. I hadn't responded to any other supplement, but Sam-E made me feel a million times better.

Three weeks later, the effects have worn off and all of my symptoms have returned. I decided to try and address the root of the problem by taking two 1000mcg Solgar Methyl-Folate last night.

I woke up at 2am feeling like someone was squeezing my heart in their fist. My shortness of breath was terrible, I couldn't take a single full-feeling breath. My anxiety and dread were horrible, terrified that I was never going to feel happy again.

It's 3pm now and I feel mostly back to "normal" (regular intensity of my usual symptoms).

Can someone please help me understand what in the world just happened? I've read that folate is a serotonin re-uptake promoter. Should I just avoid it? And if so, then how can I get to the root of my methylation issues?

I want to help my siblings too. We used to be so fun-loving, social, successful, competitive, happy, and energetic in high school. Now we're all just miserable.

Thank you!

 

[Critterina]

@Tor,

Sounds like you might have survived a heart attack. Seriously. It also reminds me of the symptoms of pulmonary embolism (blood clot in the lungs) and of dehydration (especially the anxiety and dread). It may have had nothing to do with what you took, so get yourself checked out. My great aunt had a heart attack but waited until the morning to call my mom for a ride to the hospital...so she wouldn't wake her up. My mom, at 89, had clots in both lungs, thought she was dehydrated, so drank a quart of water before going to exercise for an hour; she was only diagnosed the NEXT DAY when she went for a pre-op. Idiocy! Go!

Of course, it's possible that it wasn't a heart attack, so AFTER you've ruled that out, and since you had good, but brief, results from SAMe, investigate methylation. Undermethylation is a broad term. You're going to have to get more specific about what is causing it, or even if that is a useful way of thinking of it, before you can figure out what to do.

Which brings me to the first point: You are right this is a great site, even for people like us without ME/CFS. But...People here can help you understand theories and suggest things you might want to look into or try, but you have to be the one responsible for what you decide to do. And for getting a medical professional that you trust and who is competent (easier said than done, as you can see on this forum!)

And here is the second point: Prepare for your methylation investigation to be a marathon of trial and error. It may take you a long time. One thing that seems to be a pattern, you supplement with one thing (SAMe), and it makes a world of difference, until you run out of the next thing in short supply - it used to be the second most scarce resource, now it's the rate-liming one. What could this be? Lots of things.

So, to specifics: You said homozygous for the MTHFR. Is it C667T or A1298C - or both? Do you have more of your genome characterized? It won't give you 'answers' but it will give you a lot more to go on. Is your homocysteine high? Have you had an amino acid panel done? Other lab tests? This is why a good doctor is so important...they can look at the whole picture. You have neurotransmitter and cardiovascular and joint issues going on. It's not easy to untangle that. Methylation may be part of the picture (or not), but it's likely not the whole picture.

Kudos to you, though, Tor, for stopping the drug/alcohol habits. That can be so difficult! Sorry not to be of more help at this point. Let us know what the doctor says about your experience last night, OK?

Best of health to you!
Critterina

 

[Tor]

Hi @Critterina , thank you so much for your reply! I'm so glad your mom & great aunt were both okay, yikes!! My doctor let me know this feeling isn't a heart attack, but instead a physical manifestation of anxiety/depression. I've had this feeling for years now (constantly, 24x7), and just keeps worsening as my mental health worsens.

The weird thing is, I have none of the usual symptoms associated with anxiety/chest tightness. No shaking, sweating, racing heart, palpitations, or choking. My doctor even tried putting me on a few beta blockers (assuming the chest tightness was physical anxiety), and all they did was make me tired. I think it's because none of my symptoms are traditional "anxiety" (over-active system), and more with an under-active system. Coffee improves/helps the dread feeling very much, which I think is the opposite for classic anxiety.

I also have constantly high blood pressure (135+). He tested for thyroid, anemia, sex hormones, etc. Nothing abnormal. To any outsider (including my doctor), I seem to be super well functioning, which is what makes this feeling so impossible to understand.

His last step was an SSRI, but he admitted it was just a guess. That's when I started digging on my own and found this forum. I'm really frightened about directly modifying my brain chemistry, so I wanted to rule other things out before giving up and going the Prozac route.

MTHFR is A1298C - when we got that result back, I ordered the full test from 23andme. I'm currently waiting for my results. I will also ask my doctor to test homocysteine and amino acids! I think he's getting annoyed that I won't just take the SSRI, but he's still working with me, so that's a good sign at least.

Thank you again for your reply, I really appreciate it!

 

[Critterina]

Hi @Tor,

Wow, that is weird! But I'm so glad it wasn't your heart or lungs. I'm also glad that you've had all these things tested already. Anxiety and depression are often associated with A1298C, but with the cardio history in your family, I was afraid that you might have the C677T also. So, the homocysteine test isn't all that important, then.

I'm hetero A1298C, which isn't supposed to affect you all that much, but I was such a melancholy child, and have had a few episodes of depression as an adult, one requiring medication. For me, anxiety and the world is going to end in the next few hours doom are associated strongly with dehydration - so I know that feeling, but I feel for you, not being able to drink a quart of water and get over it.

Comments in sympathy: I had one doctor look at my labs and be very happy with how good the numbers are; then someone else who was really trying to help me confessed that she really didn't usually work with people who were as sick as I was. Same lab results. So, as you know, your numbers can be good and you can still be messed up.

I think that overall it's going to be a good thing to get those 23andMe results. Some of the stuff I'm thinking of now is: what's your B12 mutations? COMT and MAO B mutations? Will you tolerate an active B complex? Do foods/drinks that say Phenylketonurics: Contains phenylalanine aggravate your anxiety? Low tyrosine diet? Do you already take Co-Q10? Do you like coconut water? Can they measure your dopamine or norepinephrine (and would it tell you anything)? Do you react to Sudafed? Perhaps your serotonin is good and it's the dopamine branch of neurotransmitters (and not really methylation) that is most messed up. I don't know!! (As if you can't tell from these questions!) Anyway, if you can and want to answer some of these - or just note other odd things you react to - feel free. I don't promise my musings to be of any help, but maybe we can come up with some good questions for your doctor.

I'd like to tag some other people to look at this thread, my go-to person Valentijn already looked, but not sure who else, as this isn't an area I've looked into much...
@Little Bluestem @caledonia @Sushi @Hip @PeterPositive @ahmo @AndyPandy @nandixon - if have ideas, or if you know who might, please chime in.

 

[caledonia]

Hi, just popping in so you can access my signature link, which has a lot more info.

What you did was flood your body with a huge amount of methylfolate with no-cofactors. You may have various SNPs or functional things happening that contribute to you not tolerating methylfolate well.

My suggestion would be to not experiment with any more methylation supps until you do a lot of research, some genetic and functional testing and/or get a good doc on board.

The homozygous A1298C is associated with mental health issues as well as addiction issues. You may also have MAO A and COMT SNPs which would also contribute.

It sounds like you may have elevated cortisol as one of your issues, in which case, lowering cortisol should be helpful.

That's interesting that Klonopin did nothing. It works on GABA, so if you had high glutamate (common for anxiety) it should have been helpful. At any rate, it's very addictive, so it's better to avoid it if possible.

Your best choices for a doc may either be a Ben Lynch practitioner or a William Walsh practitioner.

http://mthfr.net/mthfr-resources/

http://www.walshinstitute.org/clinical-resources.html

 

[Tor]

Thank you again @Critterina! Your kind & detailed responses mean the world to me. I can't wait to hear back from 23andme as well!

My brothers both dealt with addictions to dopamine-boosting stuff (amphetamines), so that might make sense! For me, a bottle of wine would provide some really wonderful temporary relief - happiness, energy, freedom, gentle, light-hearted, imaginative. But then of course next day would feel horrendous. Not even hangover symptoms, just absolutely miserable mentally. And the good effects got less and less the more I did it.

When I first started taking 400mg/5-HTP per day, I was feeling a little better. Similar to SamE, it's not doing much any more.

I could try a Sudafed tomorrow to see how that feels! Or coconut water tonight, what might that test?

It's weird, for the first 20 years of my life I had so much positive energy all the time. Never a single issue with mental health in high school - I was always happy. Then in college, I introduced a morning coffee, some drinking, and an emotional trauma - no idea which screwed up my balance, but I would give anything to go back to my past state.

Thank you again!

 

[Tor]

Thank you @caledonia , these are some wonderful resources! As you learned more about your SNPs and methylation, did the corresponding treatment improve your symptoms? I just want to make sure I'm heading down a helpful path - I know I can be sort of impatient

My cortisol test showed this:

Cortisol (Saliva - Morning) 10.5 H ng/mL. Range: 3.7-9.5
Cortisol (Saliva - Noon) 1.6 ng/mL. Range: 1.2-3.0
Cortisol (Saliva - Evening) 2.4 H ng/mL. Range: 0.6-1.9
Cortisol (Saliva - Night) 0.9 ng/mL. Range: 0.4-1.0

The chest squeezing is constant (haven't not felt it in 5 years), so if it was cortisol related, wouldn't there be some relief around noon / night when my cortisol seems to drop?

 

[Dazey]

Hi @Tor

I'm a newbie here but have been lurking for several months.

I've suffered most of the symptoms you described in your first post for most of my life (I'm middle aged now) and wanted to let you know that I've found significant relief from following @Freddd's active B12 protocol (found on this forum).

I know the feeling of dread you describe intimately! This protocol is the first treatment that's lifted it for any length of time. Psych meds and therapies have been worse than useless for me. I've experienced a placebo effect from some of them, but it's never lasted for more than a couple of weeks. I've been feeling a lot brighter for months now since starting Freddd's protocol (thank you so much Freddd ).

I still suffer from anxiety, but because I'm not constantly dwelling on dark thoughts caused by a sense of impending doom, the anxiety has greatly eased. And the protocol is still very much a work in progress for me!

I was lucky that I was able to increase methylfolate fairly rapidly (when all the co-factors such as a good B complex were in place, and also methyl B12 and potassium), but from my extensive research of this forum it seems that some people have to titrate incredibly slowly a crumb at a time or they experience some very unpleasant symptoms.

There are other methylation treatment plans to choose from, so definitely listen to the expert forum members about doing your research and treading very carefully. Good luck!

 

[Tor]

Hi @Dazey , your reply gave me so much hope! I've almost never had anyone say "hey me too" when I describe my symptoms (more "uhh wtf"). I'm so glad you've found answers and relief from your dread feeling. It sounds like the methylation protocol has given your mind/body the tools it needs to keep healing from the anxiety. Because when something is wrong with our bodies, no amount of meditation or mindfullness can cure those feelings.

Can I ask how long you've been on Fredd's protocol, and how long it took to start noticing positive effects? I will definitely try to be patient and wait for my other test results before making any changes

 

[Dazey]

Hi @Dazey , your reply gave me so much hope! I've almost never had anyone say "hey me too" when I describe my symptoms (more "uhh wtf"). I'm so glad you've found answers and relief from your dread feeling. It sounds like the methylation protocol has given your mind/body the tools it needs to keep healing from the anxiety. Because when something is wrong with our bodies, no amount of meditation or mindfullness can cure those feelings.

I'm so glad my post helped @Tor!

The sentence I've bolded really rings a bell for me because that's exactly how I've felt for years! My psychiatrists/psychologists refused to listen though.

Can I ask how long you've been on Fredd's protocol, and how long it took to start noticing positive effects? I will definitely try to be patient and wait for my other test results before making any changes

I'm not sure exactly how long I've been doing this because I didn't keep a diary at first (it's important to keep a diary to keep track of symptoms). I think about 4-5 months? The improvement was gradual but I think it's been there from the beginning. It's hard to tell sometimes because it's a very steep learning curve to keep track of the side effects and learn how to treat them (usually by increasing methylfolate, methylB12 or potassium). Research is key to this!

I've found a sweet spot where I'm not getting any side effects for the moment so I'm very happy about that, but I've still got a long way to go to heal completely.

I don't want to give you false hope that Freddd's system will work for you though. It's helped a lot of people on this forum, but not everyone. If it doesn't, there are other methylation protocols that might suit you better. I'm sure there's an answer for you though!

 

[Dazey]

To save you some time, here's a couple of up-to-date guides to Freddd's protocol l've found very helpful (a big thank you to @ahmo and @sheclimber ):

@ahmo's guide: http://forums.phoenixrising.me/index.php?entries/a-guide-to-freddds-protocol.1618/

@sheclimber's guide: http://forums.phoenixrising.me/index.php?entries/my-understanding-of-freddds-protocol.1697/

 

[Tor]

Hi @Dazey , @Critterina , and @caledonia , I got my 23andme results today! I was wondering if you might be able to interpret this better than me? I'm so hopeful that I have clues now. Thank you in advance!

First off, MTHFR is compound heterozygous, not homozygous! I called my doctor to confirm, he said the same thing:

MTHFR C677T +/-
MTHFR A1298C +/-

I'm also homozygous for the following:

VDR Taq +/+
MAO A R297R +/+
MTRR A664A +/+

Heterozygous for another MTRR:
MTRR A66G +/-

And heterozygous for two CBS:
CBS C699T +/-
CBS A360A +/-

Does this help to explain any of my symptoms, and is there any hope for nutrition or protocol that can get me on the right track?

Thank you!

 

[caledonia]

Just a quick note, click on my signature link to go to the SNPs Interpretation Guide. Note that SNPs info should be combined with functional testing to design an individualized protocol. I have several other useful documents.

 

[caledonia]

ps. I see I missed one of your tags. I will get back with a closer look at things.

 

[Tor]

@caledonia this guide is SO helpful, thank you!!! I love this forum!

 

[Dazey]

Hi @Tor

I can't be of any help to you with genetic testing, but I hope you find the answers you need (it sounds like you're well on your way). Keep us updated won't you? Good luck!

 

[caledonia]

Thank you @caledonia , these are some wonderful resources! As you learned more about your SNPs and methylation, did the corresponding treatment improve your symptoms? I just want to make sure I'm heading down a helpful path - I know I can be sort of impatient

My cortisol test showed this:

Cortisol (Saliva - Morning) 10.5 H ng/mL. Range: 3.7-9.5
Cortisol (Saliva - Noon) 1.6 ng/mL. Range: 1.2-3.0
Cortisol (Saliva - Evening) 2.4 H ng/mL. Range: 0.6-1.9
Cortisol (Saliva - Night) 0.9 ng/mL. Range: 0.4-1.0

The chest squeezing is constant (haven't not felt it in 5 years), so if it was cortisol related, wouldn't there be some relief around noon / night when my cortisol seems to drop?

Your cortisol is out of range high in the morning, and evening, and trending high at night. You may want to do some Seriphos or Relora as well as stress reduction techniques to lower your cortisol. This should help you feel less anxious and may help those middle of the night wakenings.

 

[Johnmac]

Two more specific things to add:

* M-folate starts body healing, & body healing sucks out potassium. Your symptoms are partly consonant with low potassium. This is extremely common on the Freddd Protocol, which uses lots of methylfolate. (Yes, caledonia's right that it may also be the co-factors you need - the B12s etc.)

* But more likely: 'Extreme internal anxiety (even though everyone thinks I'm "so calm" on the outside)' is a - perhaps the - classical symptom of pyroluria. 'Constant tightness / dread in chest' and 'Extreme irritability at trivial things, especially noises' are also hallmark pyroluria symptoms.

You definitely should check out pyroluria. The urine test is maybe $100. Or you could just start taking the supps & see what happens. For me it has been the easiest illness yet to treat.