Methylation Supplementation - Seeming Loss of Effectiveness

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I'm looking for advice on what to do regarding methylation supplementation. I see tons and tons of resources regarding it on here, but it honestly is all very overwhelming and I find myself uncertain.

I recently started taking 7.5mg l-Methylfolate along with 50mg B6, and 500mg Vitamin C (also 100mg 5-HTP 3x/day but I assume it doesn't relate to this much) as prescribed by my psychiatrist to address findings from a recent organic acids test. For the first few days on the methylfolate I experienced a noticeable increase in energy and general motivation but I've noticed the effects have subsided after less than a week of use. I imagine this means I am lacking in some other methylation requirement?

I know potassium is important and have (I think) experienced the effects of not having enough recently. I have been mindful to include potassium-rich foods in my diet and have not since experienced potassium deficiency.

I see B12 mentioned a lot, but it seems to be more-so something you should take to ensure you don't have masked B12 deficiency which I recognize is important but unless I'm mistaken doesn't entirely relate to my concerns at the moment.

I also found this https://me-pedia.org/wiki/Methylation_cycle_hypothesis#Freddd.27s_Protocol which seems to be a synopsis of Freddd's protocol which I've seen mentioned here a lot. I don't really feel comfortable following it completely since I have been prescribed the medications I'm currently on explicitly by my psychiatrist.

My current thinking is to add the "basic cofactors" section onto my current regimen one by one to try and find which one or multiple I may be additionally deficient in. I have no idea if this is a good idea though and would love some feedback from those with more experience and knowledge. Also, if anyone has any insight into what doses are recommended that would also be very helpful as it seems some of the supplements listed don't mentioned this.
 

Judee

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Not regarding methylation because I don't understand much of it myself but just wanted to say I would be careful with the 5-HTP if your doctor also has you on an SSRI.

I think Julia Ross cautioned about Serotonin Syndrome with taking some of those supplements with Rx meds.

Just a thought.

Edit: Also I would make sure you have any infections under control before trying methylation. One YT doctor that talked about SIBO said that bacteria methylate too. He said that taking those kind of supplements before getting the bacteria under control is just "fertilizing them."

I think that also happens with iron supplements as well. When we have an infection, our body tries to hide the iron from the bacteria by storing it as ferritin. At least, that is my understanding.
 
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drmullin30

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@Wyverngale, I've been doing methylation protocols for well over ten years and it wasn't until I got my genetic profile and tailored my supplements and program to my genetics that I finally found any real success.

I am currently doing Freddd's protocol with genetic tailoring to my specific genetic needs and I can honestly say I am in the best health of my life but my genetic profile and list of SNPS was crucial to getting here.

Your genetic profile can also inform your dosing and how much build up and damage you might be dealing with. A lifelong b12 or folate deficiency will take many years to heal from and if you have severe genetic metabolic deficiencies, this could be the case.

As you can see from the link you provided, the methylation cycle is very complex and many supplements will accelerate or decelerate the cycle at various points so in my opinion, it's very important to know your genetics and to know in which parts of the cycle you have single nucleotide polymorphisms or SNPs that may be impacting your metabolism.

This information will tell you which methyl donors and supplements you might want to concentrate on e.g. folate, b12, b6, TMG, ALCAR, NAC, molybdenum etc. There can be treatment conflicts between SNPs that will hinder or stop progress.

Methylation is also tied up with other vitally important metabolic cycles such as sulfuration, glycosylation and Phase 1 and Phase II detoxification. Your genetic profile can give you information about those cycles as well.

I've attached one of Amy Yasko's books which helps explain some of this.

If you haven't yet, I would also take a serious look at your diet for triggers. Gluten, dairy, oxalate, sugar SIBO, etc. can all exasperate health problems associated with methylation.

My diet is grain free, gluten free, dairy free, sugar free, alcohol free, low oxalate, ketogenic paleo diet. I eat no processed foods or additives and this has also been crucial for my healing. Gluten and oxalates in my case drove a lot of my health problems. Oxalates can wreak havoc with methylation see here:

https://mthfrsupport.com/2018/03/understanding-sulfation-and-oxalate/

Hope this helps, don't hesitate to reach out if you want to discuss more.
 

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@Judee I appreciate the warnings. I am not taking any SSRIs nor do I have any infections.

@drmullin30 Thanks for the book and the advice. I guess I'll have to get in touch with my psychiatrist to see if they can get a methylation pathway test for me.

In the meantime I think I'm going to have to stop taking the methylfolate sadly. The past couple days have been pretty rough and I'm guessing it's due to that.
 
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On account of MCAS, I am allergic to most methylation supplements. However, I was able to take DMG without an allergic reaction. For several days the DMG helped me for a few hours hours after each dose. By the end of a week, it stopped working. I do not know why.

Instead of a high dose methylation protocol, seeking a methylation balance may be more advantageous. Quoting from https://kresserinstitute.com/treating-methylation-supplementing/

"Methylation should first and foremost be addressed by making diet and lifestyle changes, addressing gut issues, and removing methylation competitors and inhibitors."

See also: https://blog.davincilabs.com/blog/is-tmg-or-dmg-more-effective

If a person does not do well on high B6, DMG, and TMG, this may indicate a person will not respond well to methylator precursors, according to: http://www.enzymestuff.com/methylation.htm
 
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This is more just venting than anything, but I stopped taking the methylfolate today and it's probably been the worst in a while for me. I've had headaches on and off throughout the day and have been basically bedridden due to fatigue. I wish this was easier. It's so frustrating to get a taste of normalcy for a few days just to have it ripped away with no clear path forward.
 

drmullin30

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@Wyverngale I know you don't think you need to supplement b12 but folate doesn't work properly without it and if you supplement folate without b12 you'll deplete your b12 stores very quickly. I don't know of anyone who used folate successfully without b12. Others on this forum may be able to explain it better but I believe they are both necessary to achieve cell penetration. The problems you experience with folate may be caused by b12 deficiency which then causes paradoxical folate deficiency. All of the symptoms you describe above can be attributed to b12 deficiency. If you are concerned about start up you can start with very small doses as many others have done.
 
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@Wyverngale I know you don't think you need to supplement b12 but folate doesn't work properly without it and if you supplement folate without b12 you'll deplete your b12 stores very quickly. I don't know of anyone who used folate successfully without b12. Others on this forum may be able to explain it better but I believe they are both necessary to achieve cell penetration. The problems you experience with folate may be caused by b12 deficiency which then causes paradoxical folate deficiency. All of the symptoms you describe above can be attributed to b12 deficiency. If you are concerned about start up you can start with very small doses as many others have done.
I actually have B12 on the way and will be trying it. It isn't that I didn't think I needed it. It's just that everything I read didn't indicate that B12 was needed in methylation so I was just trying to focus on methylation since my problems were coming after I started taking methylfolate. I assumed it was a lack of any of the handful of chemicals used in methylation. Also, since I have seen repeatedly that methylfolate masks symptoms of B12 deficiency I figured if I was dealing with that then it wouldn't be the problem at the forefront.

If what you say is true then I guess I will reattempt the methylfolate after my B12 comes in. If you have any resources to show what you're talking about I'd appreciate it.