• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

Poor Methylation Reaction - Tingling Legs, Increased Heart Rate, Depression

Oberon

Senior Member
Messages
214
Hi Everyone,

I was hoping to get some second opinions on what may have caused some of my recent issues. I have been playing around with methylation for almost a year and had some improvements in energy and mental state up until this year so I took a break from methylfolate and maintained my other supplements.

I am always continuously tweaking things based on things I read and the advice of this forum and It appears I've screwed something up rather badly this time around. I started taking methylfolate again this week (aside from what's in my B-Complex) and wound up with the following symptoms:

1. Extreme depression (psych ward level)
2. Tingling legs
3. Racing thoughts
4. Palpitations
5. Anxiety

My dosage was ramped up from 800mcg to 6000mcg over the span of two weeks. Other supplements I've been taking are the following:

1 B12Oils spray of Methyl/Adenosyl
1 Swanson Bioavalable B-Complex
1 Tablespoon of Jarrow Liquid Carnitine
5000IU Vitamin D
200mg Selenium
200mg Magnesium
Low dose multi-mineral complex
Low dose Iodine

All of the above I have been taking for at minimum 2 months (some for years) and haven't had any major reactions to them.

The only major differentiating factor is the Methylfolate, but where things are interesting I used to be able to take 15mg of Metafolin without any major issues and found it really helped with my depression. (I am homozygous MTHFR C677T)
_________________________________________

The other confusing factor is this is not the first time this has happened. This also happened in January 2016 where I tried a similar experiment with Methylfolate and wound up in the ER taking ativan on a daily basis until things wound down.
_________________________________________

My first instinct is potassium, but my results have been within range including when I had my blood test today 3.9 (Range of 3.5-4.9). I tried taking 200mg of Potassium today and it seemed to make the problem worse rather than better. This is also what happened back in January where I seemed to have developed a permanent acid reflux problem from taking potassium.

One other thought was I tried taking Niacin to damper things down which seemed to work until 4 hours later where everything went haywire again and the depression was way worse.
_________________________________________

Right now I'm still feeling fairly depressed and have tingling legs. My heart rate has mostly normalized. I'll probably be taking ativan again for a few days in hope things calm down.

The only thing that was elevated on my bloodwork today was my Creatinine level, which I'm not sure could explain this.

Any thoughts or opinions on what may have caused this would be tremendously appreciated, especially on the extreme depression front.
 

Deltrus

Senior Member
Messages
271
Your symptoms remind me of copper dumping, overmethylation, or hyperthyroidism. I'm not an expert though and it's just a bit of speculation.

Usually if you get huge sudden side effects from supplements then, if you stop, you will slowly return back to normal.

Good luck hanging on through the depression storm until then! I know your pain.
 

skwag

Senior Member
Messages
222
Hi lakesarecool,

Sorry to hear about your troubles. My first guess would be potassium too. Many people have reported symptoms of low potassium with values higher than 3.9. What type of potassium were you taking that caused the acid reflux?

At the time you were able to tolerate 15mg methyfolate, were you also taking the b12oils and the liquid carnitine, or is that new?
 

Oberon

Senior Member
Messages
214
Hi Deltrus and Skwag,

Thank you for the feedback and kind words,

The potassium I was taking was Potassium Citrate which gave me the reflux problem. I've tried switching to Gluconate and Bicarbonate and don't seem to react well to either of them. My final attempt was coconut water which also seemed to induce reflux.

Something about me and potassium don't seem to get along too well.
_____
In January I was taking the B12 Oils, with methylfolate without issue. It was the carnitine that I added that seemed to really start the whole crisis. This time around I've been taking B12 Oils and carnitine without the folate and it seemed adding the folate triggered this attack.
_____
It almost seems like getting my methylation cycle going is zapping my body of all its needed neurotransmitters. Maybe I need to try much much lower doses of everything in a few months once I'm out of this whole mess.
 

Oberon

Senior Member
Messages
214
So it's been about a month since my initial attack and I think it's important to have an update for anyone else considering embarking on a methylation journey. I have had the unenjoyable opportunity to learn methylation supplements can be really powerful and I'm starting to regret my more lax attitude with dosages and not paying enough attention to side effects.

It seems I am permanently worse off since I began methylation (I haven't taken methyl donors since my original post) with the following symptoms:

Increased general anxiety and insomnia
Depression and Anhedonia
Constant wired but tired feeling
Dysphagia and regurgitation
Stiff Muscles
Acid Reflux
Constipation
Gastroparesis
Brain Fog
Increased overall pain and inflammation
Much lower energy levels

I believe that I may have either induced a serious deficiency in something along the way or greatly increased the level of inflammation in my body which I have been unable to recover from.

I know methylation protocols have helped many people on this site, but I want to really urge others to proceed with major caution when it comes to methylation and understand that you may very well wind up worse off without necessarily recovering rather than better.
 

Deltrus

Senior Member
Messages
271
Have you tried large amounts of methyl donors such as TMG? One time I had similar symptoms to yours, and it took around 8g of TMG to fix them. Sometimes methylfolate needs more methyl groups than it provides. It would line up, I just read you haven't taken any methyl donors at all.

I had extremely stiff muscles, no energy, extreme anhedonia, constipation, anxiety and insomnia for like 1.5 weeks, all fixed by TMG.

I only figured it out because I normally take 1.5g TMG every day with my supplements, then I realized I stopped, and the next week I got those symptoms.

I didn't make the connection in the first post because I didn't see anything about inflamed stiff muscles, insomnia, and constipation.

Also maybe try magnesium until you start getting diarrhea. At the very least it will cure your constipation for a day XD. Sometimes I get your symptoms when I need lots of magnesium.
 
Last edited:

Oberon

Senior Member
Messages
214
Thanks Deltrus, I gave it a shot today taking 500mg of TMG and the only effect so far has been a massive headache. Did you take 8g of TMG in one go or was it progressive? I may try a higher dose tomorrow as I would love to find a way out of this mess.

I've ramped up to 400mg supplemental magnesium and will keep adding some every day to see if it helps.
 

JES

Senior Member
Messages
1,320
It seems I am permanently worse off since I began methylation (I haven't taken methyl donors since my original post) with the following symptoms:

Yep, it's unfortunate and doesn't seem to be that uncommon to have this reaction to methylation supplements. Some people manage to improve especially on MB12, but those who already are prone to anxiety seem to do worse.

I tried to push through this phase of increased anxiety, fatigue, nerve pain etc., but I didn't improve at all over the course of a couple of months. I didn't even have a go at methylfolate, as that is supposedly the methyl supplement causing the most agitation and anxiety. Even a small dose of MB12 produced similar symptoms in me. Magnesium should be a really good supplement to calm brain "excitotoxicity", as are the anti-anxiety supplements mentioned in this thread.
 

Deltrus

Senior Member
Messages
271
Thanks Deltrus, I gave it a shot today taking 500mg of TMG and the only effect so far has been a massive headache. Did you take 8g of TMG in one go or was it progressive? I may try a higher dose tomorrow as I would love to find a way out of this mess.

I've ramped up to 400mg supplemental magnesium and will keep adding some every day to see if it helps.

I tend to not respond much to methyl donors, I took it all in one go. I've never had a bad response from purely TMG so I wasn't scared, I just wanted to keep taking stuff until my very bad symptoms went away. If you get a bad response to TMG then it probably isn't the answer.
 

Oberon

Senior Member
Messages
214
Thanks for all the help JES and Deltrus. I think it goes to show that this whole methylation thing is much trickier than it may seem at first glance. It's easy to think that these are all just supplements and won't have any too detrimental effects, but after my experience and reading about some others approaching a methylation protocol has some legitimate risk to it all.

I will probably do what you've done Deltrus and keep playing with lower doses of supplements hoping that I can find one that sticks and gets me some improvement as I don't seem to be recovering on my own.
 

Oberon

Senior Member
Messages
214
As an update to my post in case anyone googles this a lot of my symptoms still appear to be permanent including the below:

Dysphagia and regurgitation
Gastroparesis
Stiff Tingling Muscles
Acid Reflux
Constipation

The Dysphagia and Gastroparesis are the worst of everything. I can't eat without food uncomfortably coming back up for hours after eating. I can no longer eat anything fibrous. It constantly feels like food is getting stuck in my throat and chest.

Since these issues started I have tried the following:

B12 (Methylcobalamin) - I readded in B12 and found in lower doses it helped to lift my anxiety, insomnia and depression. It does however aggravate my dysphagia and now appears to also give me toe pain which I think may be gout (never had before).

Methylfolate - No real discernible reaction except for at certain points giving me increased energy and at other points increased weakness. I may still try adding in higher doses.

Potassium Gluconate - I learned the hard way to stay far away from Potassium Gluconate. I believe I am very sensitive to it and shortly after taking even small doses my heart rate spikes and I experience sensations of panic. I have trialed Chloride and Bicarbonate without any issues aside from some contradictory increased muscle stiffness which tells me my body may simply not like potassium supplements.

Niacinamide - I believe this may have been the cause of my extreme depression. Niacin seems to have a depressive effect on me. I find it helps me sleep and calms me down if I take too much B12, but I always wind up depressed very shortly after.

Magnesium - No discernible difference

Vitamin C - No discernible difference
_______________________________________

My life has been severely impacted through trialing methylation for the worse. At this point I'm not even sure what I can try next and keep trying to find out if there is something along the methylation cycle I may have depleted in hopes of finding some relief but so far no such luck.
 
Messages
60
Location
Michigan
@lakesarecool
...
I'm thinking that maybe you might need to add some sea salt/sodium to balance out the potassium? Especially since youre likely to have exhausted adrenals, like most of us here :( sorry if I'm assuming too much, though. I too get the tingling nerve sensations. Almost like an internal tremor exclusively in my left foot and left calf muscle when I piss off the methylation gods. Lol.

Also, are you familiar with @Freddd 's "Deadlock Quartet"? Adding the carnitine in with the other things may have opened up Pandora's box. I've done that on accident, twice. Ii felt suicidal, depressed, tingling nerve sensations, felt like all my neurotransmitters were depleted... Racing heart, wired but tired... Basically the symptoms you've described for yourself.
 
Messages
60
Location
Michigan
@lakesare...
More on Deadlock Quartet:

http://forums.phoenixrising.me/inde...y-deadlock-quartet-and-other-nutrients.27482/

Screenshot_2016-09-12-20-38-11.png
 

Oberon

Senior Member
Messages
214
@lakesarecool
...
I'm thinking that maybe you might need to add some sea salt/sodium to balance out the potassium? Especially since youre likely to have exhausted adrenals, like most of us here :( sorry if I'm assuming too much, though. I too get the tingling nerve sensations. Almost like an internal tremor exclusively in my left foot and left calf muscle when I piss off the methylation gods. Lol.

Also, are you familiar with @Freddd 's "Deadlock Quartet"? Adding the carnitine in with the other things may have opened up Pandora's box. I've done that on accident, twice. Ii felt suicidal, depressed, tingling nerve sensations, felt like all my neurotransmitters were depleted... Racing heart, wired but tired... Basically the symptoms you've described for yourself.

Hi Frenchmoxie,

I always appreciate any suggestions and the time you've taken to try and help me. I feel for you, the tingling and twitches are very frustrating!

My attempts at the deadlock quartet appears to have gone poorly. I'm sure it has worked great for several people and I may even try it again in hopes of correcting some imbalance I may have caused, but for now I'm going to hold off.

As a further updated I've completed a colonoscopy and endoscopy and the results came back clear. My most prominent symptom at this point has to be the dysphagia and difficulty swallowing with food coming back up hours after eating. Aside from that it's the tingling legs.
 
Messages
60
Location
Michigan
Hi Frenchmoxie,

I always appreciate any suggestions and the time you've taken to try and help me. I feel for you, the tingling and twitches are very frustrating!

My attempts at the deadlock quartet appears to have gone poorly. I'm sure it has worked great for several people and I may even try it again in hopes of correcting some imbalance I may have caused, but for now I'm going to hold off.

As a further updated I've completed a colonoscopy and endoscopy and the results came back clear. My most prominent symptom at this point has to be the dysphagia and difficulty swallowing with food coming back up hours after eating. Aside from that it's the tingling legs.

Hey there,

You're welcome.
But what I was thinking was that you might have inadvertently opened up some pathway or blockage with the Deadlock Quartet. That's the sickest I've ever gotten from any of my methylation experiments. Luckily I remembered reading about it on this site.
Im not sure if you were taking adenosylB12 too, but when you mentioned the carnitine addition (I think?) Was when your symptoms increased? Sorry if I'm mistaken, however .
 
Messages
60
Location
Michigan
@lakesarecool ...

Ok, just went back and read the thread. Yup. You said:
"
January I was taking the B12 Oils, with methylfolate without issue. It was the carnitine that I added that seemed to really start the whole crisis."

I think you just activated something with the Deadlock Quartet:
AdenosylB12, methylB12, methylfolate, and the Carnitine (i think the form that "works" for this deadlock purpose is carnitine Fumarate)...

Anyways, i know you said you had increased the methylfolate and that's when things got worse this time around. Just my two cents.

Also. Have you had your sodium levels looked at?
 

Oberon

Senior Member
Messages
214
Thanks for all the help frenchmoxie; Ben Lynch artilces are always a good read.

I did have my sodium levels checked and all came back clear. I also recently had another colonoscopy and endoscopy to see if something was up with my stomach and it came back clear so there's no completely detectable reason for why this is happening.

Just to experiment I tried taking B12oils again after taking a long supplement break and it instantly made me feel worse. 20 seconds after taking it I felt a sensation of something being stuck in my throat and for the rest of the day my Dysphagia (difficulty swallowing) has been twice as bad.

Now I'm thinking maybe I'm reacting to B12, while I never used to previously. I really think I've depleting something else through taking B12 but so far I've had no luck figuring out what it is. I've tried B2, Methylfolate, Magnesium, Potassium, Calcium, P5P, Selenium, Iodine to see if there's any symptom relief and haven't had success.

I'm going to keep experimenting and hope something sticks.
 

Eastman

Senior Member
Messages
526
As an update to my post in case anyone googles this a lot of my symptoms still appear to be permanent including the below:

Dysphagia and regurgitation
Gastroparesis
Stiff Tingling Muscles
Acid Reflux
Constipation

The Dysphagia and Gastroparesis are the worst of everything. I can't eat without food uncomfortably coming back up for hours after eating. I can no longer eat anything fibrous. It constantly feels like food is getting stuck in my throat and chest.

I know you've mentioned before that you've had your thyroids tested but have you tested them since you had dysphagia and gastroparesis? Some papers that may be of interest.

Does Hypothyroidism Affect Gastrointestinal Motility?

Consequences of dysthyroidism on the digestive tract and viscera
 

Oberon

Senior Member
Messages
214
@Eastman I haven't had my thyroid tested, but based on the articles it might be smart to get it checked. I will update next time I see the doctor, thank you.